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Wikipedia

Bromazepam

May 01, 2024

Bromazepam, sold under many brand names, is a benzodiazepine. It is mainly an anti-anxiety agent with similar side effects to diazepam. In addition to being used to treat anxiety or panic states, bromazepam may be used as a premedicant prior to minor surgery. Bromazepam typically comes in doses of 3 mg and 6 mg tablets.[4]

Bromazepam
Clinical data
Trade namesLexotan, Lexotanil, others
AHFS/Drugs.comMicromedex Detailed Consumer Information
Addiction
liability		High[1]
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability84%
Protein binding70%
MetabolismLiver: P450
Metabolites3-hydroxybromazepam
Elimination half-life12–20 hours (avg. 17hr)[3]
ExcretionUrine 69%, as metabolites[1]
Identifiers
  • 7-bromo-5-(pyridin-2-yl)-1H-benzo[e][1,4]diazepin-2(3H)-one
CAS Number
  • 1812-30-2 Y
PubChem CID
  • 2441
DrugBank
  • DB01558 Y
ChemSpider
  • 2347 Y
UNII
  • X015L14V0O
KEGG
  • D01245 Y
ChEBI
  • CHEBI:31302
ChEMBL
  • ChEMBL277062 Y
CompTox Dashboard (EPA)
  • DTXSID40171081
ECHA InfoCard100.015.748
Chemical and physical data
FormulaC14H10BrN3O
Molar mass316.158 g·mol−1
3D model (JSmol)
  • Interactive image
  • C1C(=O)NC2=C(C=C(C=C2)Br)C(=N1)C3=CC=CC=N3
  • InChI=1S/C14H10BrN3O/c15-9-4-5-11-10(7-9)14(17-8-13(19)18-11)12-3-1-2-6-16-12/h1-7H,8H2,(H,18,19) Y
  • Key:VMIYHDSEFNYJSL-UHFFFAOYSA-N Y
  (verify)

It was patented in 1961 by Roche and approved for medical use in 1974.[5]

Medical uses edit

Medical uses include treatment of severe anxiety.[6] Despite certain side effects and the emergence of alternative products (e.g. pregabalin), benzodiazepine medication remains an effective way of reducing problematic symptoms, and is typically deemed effective by patients[7][8] and medical professionals.[9][10][11] Similarly to other intermediate-acting depressants, it may be used as hypnotic medication[12] or in order to mitigate withdrawal effects of alcohol consumption.[13][14][15]

Pharmacology edit

 
50 Pills of Lexotanil (containing 6 mg of Bromazepam apiece) as sold by Hoffmann-La Roche in Germany

Bromazepam is a "classical" benzodiazepine; other classical benzodiazepines include: diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, flurazepam, and clorazepate.[16] Its molecular structure is composed of a diazepine connected to a benzene ring and a pyridine ring, the benzene ring having a single nitrogen atom that replaces one of the carbon atoms in the ring structure.[17] It is a 1,4-benzodiazepine, which means that the nitrogens on the seven-sided diazepine ring are in the 1 and 4 positions.

Bromazepam binds to the GABA receptor GABAA, causing a conformational change and increasing the inhibitory effects of GABA. It acts as a positive modulator, increasing the receptors' response when activated by GABA itself or an agonist (such as alcohol). As opposed to barbital, BZDs are not GABA-receptor activators and rely on increasing the neurotransmitter's natural activity.[18] Bromazepam is an intermediate-acting benzodiazepine, is moderately lipophilic compared to other substances of its class[19] and metabolised hepatically via oxidative pathways.[20] It does not possess any antidepressant or antipsychotic qualities.[21]

After night time administration of bromazepam a highly significant reduction of gastric acid secretion occurs during sleep followed by a highly significant rebound in gastric acid production the following day.[22]

Bromazepam alters the electrical status of the brain causing an increase in beta activity and a decrease in alpha activity in EEG recordings.[23]

Pharmacokinetics edit

Bromazepam is reported to be metabolized by a hepatic enzyme belonging to the Cytochrome P450 family of enzymes. In 2003, a team led by Oda Manami at Oita Medical University reported that CYP3A4, a member of the Cytochrome P450 family, was not the responsible enzyme since itraconazole, a known inhibitor of CYP3A4, did not affect its metabolism.[24] In 1995, J. van Harten at the Solvay Pharmaceutical Department of Clinical Pharmacology in Weesp reported that fluvoxamine, which is a potent inhibitor of CYP1A2, a less potent CYP3A4 inhibitor, and a negligible inhibitor of CYP2D6, does inhibit its metabolism.[25]

The major metabolite of bromazepam is hydroxybromazepam,[24] which is an active agent too and has a half-life approximately equal to that of bromazepam.[citation needed]

Side-effects edit

Bromazepam is similar in side effects to other benzodiazepines. The most common side effects reported are drowsiness, sedation, ataxia, memory impairment, and dizziness.[26] Impairments to memory functions are common with bromazepam and include a reduced working memory and reduced ability to process environmental information.[27][28][29] A 1975 experiment on healthy, male college students exploring the effects of four different drugs on learning capacity observed that taking bromazepam alone at 6 mg 3 times daily for 2 weeks impaired learning capacities significantly. In combination with alcohol, impairments in learning capacity became even more pronounced.[30] Various studies report impaired memory, visual information processing and sensory data and impaired psychomotor performance;[31][32][33] deterioration of cognition including attention capacity and impaired co-ordinative skills;[34][35] impaired reactive and attention performance, which can impair driving skills;[36] drowsiness and decrease in libido.[37][38] Unsteadiness after taking bromazepam is, however, less pronounced than other benzodiazepines such as lorazepam.[39]

On occasion, benzodiazepines can induce extreme alterations in memory such as anterograde amnesia and amnesic automatism, which may have medico-legal consequences. Such reactions occur usually only at the higher dose end of the prescribing spectrum.[40]

Very rarely, dystonia can develop.[41]

Up to 30% treated on a long-term basis develop a form of dependence, i.e. these patients cannot stop the medication without experiencing physical and/or psychological benzodiazepine withdrawal symptoms.

Leukopenia and liver-damage of the cholestatic type with or without jaundice (icterus) have additionally been seen; the original manufacturer Roche recommends regular laboratory examinations to be performed routinely.

Ambulatory patients should be warned that bromazepam may impair the ability to drive vehicles and to operate machinery. The impairment is worsened by consumption of alcohol, because both act as central nervous system depressants. During the course of therapy, tolerance to the sedative effect usually develops.

Frequency and seriousness of adverse effects edit

As with all medication, the frequency and seriousness of side-effects varies greatly depending on quantities consumed.[42][43] In a study about bromazepam's negative effects on psychomotor skills and driving ability, it was noted that 3 mg doses caused minimal impairment.[44] It also appeared that impairment may be tied to methods of testing more so than on the product's intrinsic activity.[45]

Moreover, side-effects other than drowsiness, dizziness and ataxia seem to be rare[46] and not experienced by more than a few percent of users. The use of other, comparable medication seems to display an identically moderate side-effect profile.[47][48][49]

Tolerance, dependence and withdrawal edit

Prolonged use of bromazepam can cause tolerance and may lead to both physical and psychological dependence on the drug, and as a result, it is a medication which is controlled by international law. It is nonetheless important to note that dependence, long-term use and misuse occur in a minority of cases[50][51][52] and are not representative of most patients' experience with this type of medication.[53][54]

It shares with other benzodiazepines the risk of abuse, misuse, psychological dependence or physical dependence.[55][56] A withdrawal study demonstrated both psychological dependence and physical dependence on bromazepam including marked rebound anxiety after 4 weeks chronic use. Those whose dose was gradually reduced experienced no withdrawal.[57]

Patients treated with bromazepam for generalised anxiety disorder were found to experience withdrawal symptoms such as a worsening of anxiety, as well as the development of physical withdrawal symptoms when abruptly withdrawn bromazepam.[58] Abrupt or over rapid withdrawal from bromazepam after chronic use even at therapeutic prescribed doses can lead to a severe withdrawal syndrome including status epilepticus and a condition resembling delerium tremens.[59][60][61]

Animal studies have shown that chronic administration of diazepam (or bromazepam) causes a decrease in spontaneous locomotor activity, decreased turnover of noradrenaline and dopamine and serotonin, increased activity of tyrosine hydroxylase and increased levels of the catecholamines. During withdrawal of bromazepam or diazepam a fall in tryptophan, serotonin levels occurs as part of the benzodiazepine withdrawal syndrome.[62] Changes in the levels of these chemicals in the brain can cause headaches, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, dysphoria, dizziness, derealization, depersonalization, numbness/tingling of extremities, hypersensitivity to light, sound, and smell, perceptual distortions, nausea, vomiting, diarrhea, appetite loss, hallucinations, delirium, seizures, tremor, stomach cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, short-term memory loss, and hyperthermia.[63][64]

Overdose edit

Main article: Benzodiazepine overdose

Bromazepam is commonly involved in drug overdoses.[65] A severe bromazepam benzodiazepine overdose may result in an alpha pattern coma type.[66] The toxicity of bromazepam in overdosage increases when combined with other CNS depressant drugs such as alcohol or sedative hypnotic drugs.[67] Similarly to other benzodiazepines however, being a positive modulator of certain neuroreceptors and not an agonist, the product has reduced overdose potential compared to older products of the barbiturate class. Its consumption alone is very seldom fatal in healthy adults.[68][69]

Bromazepam was in 2005 the most common benzodiazepine involved in intentional overdoses in France.[70] Bromazepam has also been responsible for accidental poisonings in companion animals. A review of benzodiazepine poisonings in cats and dogs from 1991 to 1994 found bromazepam to be responsible for significantly more poisonings than any other benzodiazepine.[71]

Contraindications edit

Benzodiazepines require special precaution if used in elderly, pregnant, child, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.[72]

Special populations edit

  • Globally, bromazepam is contraindicated and should be used with caution in women who are pregnant, the elderly, patients with a history of alcohol or other substance abuse disorders and children.
  • In 1987, a team of scientists led by Ochs reported that the elimination half-life, peak serum concentration, and serum free fraction are significantly elevated and the oral clearance and volume of distribution significantly lowered in elderly subjects.[73] The clinical consequence is that the elderly should be treated with lower doses than younger patients.
  • Bromazepam may affect driving and ability to operate machinery.[74]
  • Bromazepam is pregnancy category D, a classification that means that bromazepam has been shown to cause harm to the unborn child. The Hoffman LaRoche product information leaflet warns against breast feeding while taking bromazepam. There has been at least one report of sudden infant death syndrome linked to breast feeding while consuming bromazepam.[75][76]

Interactions edit

Cimetidine, fluvoxamine and propranolol causes a marked increase in the elimination half-life of bromazepam leading to increased accumulation of bromazepam.[73][77][25]

Society and culture edit

Drug misuse edit

See also: Benzodiazepine use disorder

Bromazepam has a similar misuse risk as other benzodiazepines such as diazepam.[78] In France car accidents involving psychotropic drugs in combination with alcohol (itself a major contributor) found benzodiazepines, mainly diazepam, nordiazepam, and bromazepam, to be the most common drug present in the blood stream, almost twice that of the next-most-common drug cannabis.[79] Bromazepam has also been used in serious criminal offences including robbery, homicide, and sexual assault.[80][81][82]

Brand names edit

It is marketed under several brand names, including, Brozam, Lectopam, Lexomil, Lexotan, Lexilium, Lexaurin, Brazepam, Rekotnil, Bromaze, Somalium, Lexatin, Calmepam, Zepam and Lexotanil.[83]

Legal status edit

Bromazepam is a Schedule IV drug under the Convention on Psychotropic Substances.[84]

Synthesis edit

 
Bromazepam synthesis.[85]

See also edit

References edit

  1. ^ a b "Bromazepam: Uses, Interactions, Mechanism of Action". DrugBank Online. Retrieved 2024-02-25.
  2. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ^ "Lexotan (bromazepam) Product Insert" (PDF). Roche. 23 October 2012.
  4. ^ "Bromazepam". Pharmaceutical Benefits Scheme (PBS). Australian Government - Department of Health. Retrieved 23 March 2014.
  5. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 53X. ISBN 9783527607495.
  6. ^ "Content Not Available". www.uptodate.com. Retrieved 2017-09-07.
  7. ^ Podiwinsky F, Jellinger K (March 1979). "[Bromazepam in the treatment of somatized psychogenic disorders (author's transl)]" [Bromazepam in the treatment of somatized psychogenic disorders]. Wiener Klinische Wochenschrift (in German). 91 (7): 240–244. PMID 34934.
  8. ^ Laxenaire M, Kahn JP, Marchand P (May 1982). "[A clinical trial of bromazepam (author's transl)]" [A clinical trial of bromazepam]. La Nouvelle Presse Médicale (in French). 11 (22): 1699–1701. PMID 6124936.
  9. ^ Ropert R, Bernes J, Dachary JM (1987). "[Efficacy and tolerance of alprazolam and bromazepam in flexible doses. Double-blind study in 119 ambulatory anxious patients]" [Efficacy and tolerance of alprazolam and bromazepam in flexible doses. Double-blind study in 119 ambulatory anxious patients]. L'Encéphale (in French). 13 (2): 89–95. PMID 2885173.
  10. ^ Hallett C, Dean BC (11 August 2008). "Bromazepam: acute benefit-risk assessment in general practice". Current Medical Research and Opinion. 8 (10): 683–688. doi:10.1185/03007998409110117. PMID 6144455.
  11. ^ "Bromazépam" (PDF). Haute Autorité de santé (HAS) (in French). 7 September 2016.
  12. ^ "Bromazepam".
  13. ^ "Bromazépam". Répertoire des Spécialités Pharmaceutiques. ANSM: Agence Nationale de Sécurité du Médicament et des Produits de Santé (French: National Security Agency of Medicines and Health Products).
  14. ^ Chweh AY, Lin YB, Swinyard EA (April 1984). "Hypnotic action of benzodiazepines: a possible mechanism". Life Sciences. 34 (18): 1763–1768. doi:10.1016/0024-3205(84)90576-9. PMID 6145073.
  15. ^ Cordingley GJ, Dean BC, Hallett C (11 August 2008). "A multi-centre, double-blind parallel trial of bromazepam ('Lexotan') and lorazepam to compare the acute benefit-risk ratio in the treatment of patients with anxiety". Current Medical Research and Opinion. 9 (7): 505–510. doi:10.1185/03007998509109625. PMID 2863089.
  16. ^ Braestrup C, Squires RF (April 1978). "Pharmacological characterization of benzodiazepine receptors in the brain". European Journal of Pharmacology. 48 (3): 263–270. doi:10.1016/0014-2999(78)90085-7. PMID 639854.
  17. ^ Bromazepam Eutimia.com - Salud Mental. © 1999-2002.
  18. ^ Poisbeau P, Gazzo G, Calvel L (11 September 2018). "Anxiolytics targeting GABAA receptors: Insights on etifoxine". The World Journal of Biological Psychiatry. 19 (sup1): S36–S45. doi:10.1080/15622975.2018.1468030. PMID 30204559.
  19. ^ Adeyemo MA, Idowu SO (25 November 2016). "Correlation of lipophilicity descriptors with pharmacokinetic parameters of selected benzodiazepines". African Journal of Biomedical Research. 19 (3): 213–218.
  20. ^ Oelschläger H (July 1989). "[Chemical and pharmacologic aspects of benzodiazepines]". Schweizerische Rundschau für Medizin Praxis (in German). 78 (27–28): 766–772. PMID 2570451.
  21. ^ Amphoux G, Agussol P, Girard J (May 1982). "[The action of bromazepam on anxiety (author's transl)]" [The action of bromazepam on anxiety]. La Nouvelle Presse Médicale (in French). 11 (22): 1738–1740. PMID 6124947.
  22. ^ Stacher G, Stärker D (February 1974). "Inhibitory effect of bromazepam on basal and betazole-stimulated gastric acid secretion in man". Gut. 15 (2): 116–120. doi:10.1136/gut.15.2.116. PMC 1412901. PMID 4820635.
  23. ^ Fink M, Weinfeld RE, Schwartz MA, Conney AH (August 1976). "Blood levels and electroencephalographic effects of diazepam and bromazepam". Clinical Pharmacology and Therapeutics. 20 (2): 184–191. doi:10.1002/cpt1976202184. PMID 7375. S2CID 38155674.
  24. ^ a b Oda M, Kotegawa T, Tsutsumi K, Ohtani Y, Kuwatani K, Nakano S (November 2003). "The effect of itraconazole on the pharmacokinetics and pharmacodynamics of bromazepam in healthy volunteers". European Journal of Clinical Pharmacology. 59 (8–9): 615–619. doi:10.1007/s00228-003-0681-4. PMID 14517708. S2CID 24131632.
  25. ^ a b van Harten J (1995). "Overview of the pharmacokinetics of fluvoxamine". Clinical Pharmacokinetics. 29 (Suppl 1): 1–9. doi:10.2165/00003088-199500291-00003. PMID 8846617. S2CID 71812133.
  26. ^ "LECTOPAM®". RxMed. Retrieved 23 March 2014.
  27. ^ Münte TF, Gehde E, Johannes S, Seewald M, Heinze HJ (1996). "Effects of alprazolam and bromazepam on visual search and verbal recognition memory in humans: a study with event-related brain potentials". Neuropsychobiology. 34 (1): 49–56. doi:10.1159/000119291. PMID 8884760.
  28. ^ Montenegro M, Veiga H, Deslandes A, Cagy M, McDowell K, Pompeu F, et al. (June 2005). "[Neuromodulatory effects of caffeine and bromazepam on visual event-related potential (P300): a comparative study]". Arquivos de Neuro-Psiquiatria. 63 (2B): 410–415. doi:10.1590/s0004-282x2005000300009. PMID 16059590.
  29. ^ Cunha M, Portela C, Bastos VH, Machado D, Machado S, Velasques B, et al. (December 2008). "Responsiveness of sensorimotor cortex during pharmacological intervention with bromazepam". Neuroscience Letters. 448 (1): 33–36. doi:10.1016/j.neulet.2008.10.024. PMID 18938214. S2CID 22491979.
  30. ^ Liljequist R, Linnoila M, Mattila MJ, Saario I, Seppälä T (October 1975). "Effect of two weeks' treatment with thioridazine, chlorpromazine, sulpiride and bromazepam, alone or in combination with alcohol, on learning and memory in man". Psychopharmacologia. 44 (2): 205–208. doi:10.1007/BF00421011. PMID 710. S2CID 36415883.
  31. ^ Stacher G, Bauer P, Brunner H, Grünberger J (January 1976). "Gastric acid secretion, serum-gastrin levels and psychomotor function under the influence of placebo, insulin-hypoglycemia, and/or bromazepam". International Journal of Clinical Pharmacology and Biopharmacy. 13 (1): 1–10. PMID 2560.
  32. ^ Bourin M, Auget JL, Colombel MC, Larousse C (1989). "Effects of single oral doses of bromazepam, buspirone and clobazam on performance tasks and memory". Neuropsychobiology. 22 (3): 141–145. doi:10.1159/000118609. PMID 2577220.
  33. ^ Puga F, Sampaio I, Veiga H, Ferreira C, Cagy M, Piedade R, Ribeiro P (December 2007). "The effects of bromazepam on the early stage of visual information processing (P100)". Arquivos de Neuro-Psiquiatria. 65 (4A): 955–959. doi:10.1590/s0004-282x2007000600006. PMID 18094853.
  34. ^ Saario I (April 1976). "Psychomotor skills during subacute treatment with thioridazine and bromazepam, and their combined effects with alcohol". Annals of Clinical Research. 8 (2): 117–123. PMID 7178.
  35. ^ Jansen AA, Verbaten MN, Slangen JL (1988). "Acute effects of bromazepam on signal detection performance, digit symbol substitution test and smooth pursuit eye movements". Neuropsychobiology. 20 (2): 91–95. doi:10.1159/000118481. PMID 2908134.
  36. ^ Seppälä T, Saario I, Mattila MJ (1976). "Two Weeks' Treatment with Chlorpromazine, Thioridazine, Sulpiride, or Bromazepam: Actions and Interactions with Alcohol on Psychomotor Skills Related to Driving". Alcohol, Drugs and Driving. Modern Trends in Pharmacopsychiatry. Vol. 11. pp. 85–90. doi:10.1159/000399456. ISBN 978-3-8055-2349-3. PMID 9581.
  37. ^ Horseau C, Brion S (May 1982). "[Clinical trial of bromazepam. Thirty-four cases (author's transl)]". La Nouvelle Presse Médicale (in French). 11 (22): 1741–1743. PMID 6124948.
  38. ^ Perret J, Zagala A, Gaio JM, Hommel M, Meaulle F, Pellat J, Pollak P (May 1982). "[Bromazepam in anxiety. Clinical evaluation (author's transl)]". La Nouvelle Presse Médicale (in French). 11 (22): 1722–1724. PMID 6124942.
  39. ^ Patat A, Foulhoux P (July 1985). "Effect on postural sway of various benzodiazepine tranquillizers". British Journal of Clinical Pharmacology. 20 (1): 9–16. doi:10.1111/j.1365-2125.1985.tb02792.x. PMC 1400619. PMID 2862898.
  40. ^ Rager P, Bénézech M (January 1986). "[Memory gaps and hypercomplex automatisms after a single oral dose of benzodiazepines: clinical and medico-legal aspects]" [Memory gaps and hypercomplex automatisms after a single oral dose of benzodiazepines: clinical and medico-legal aspects]. Annales Médico-Psychologiques (in French). 144 (1): 102–109. PMID 2876672.
  41. ^ Pérez Trullen JM, Modrego Pardo PJ, Vázquez André M, López Lozano JJ (January 1992). "Bromazepam-induced dystonia". Biomedicine & Pharmacotherapy. 46 (8): 375–376. doi:10.1016/0753-3322(92)90306-r. PMID 1292648.
  42. ^ "LEXOMIL - Bromazépam - Posologie, Effets secondaires, Grossesse".
  43. ^ "How to Manage Common Drug Side Effects".
  44. ^ Hobi V, Dubach UC, Skreta M, Forgo I, Riggenbach H (25 June 2016). "The subacute effect of bromazepam on psychomotor activity and subjective mood". The Journal of International Medical Research. 10 (3): 140–146. doi:10.1177/030006058201000302. PMID 6124470. S2CID 25165191.
  45. ^ Hobi V, Dubach UC, Skreta M, Forgo J, Riggenbach H (25 June 2016). "The effect of bromazepam on psychomotor activity and subjective mood". The Journal of International Medical Research. 9 (2): 89–97. doi:10.1177/030006058100900201. PMID 6112173. S2CID 21899896.
  46. ^ "Side effect information for Bromazepam".
  47. ^ "Side effect information for Lorazepam".
  48. ^ "Side effect information for Diazepam".
  49. ^ "Notice patient - LORAZEPAM MYLAN 1 mg, comprimé pelliculé sécable - Base de données publique des médicaments".
  50. ^ Yen CF, Ko CH, Chang YP, Yu CY, Huang MF, Yeh YC, et al. (September 2015). "Dependence, misuse, and beliefs regarding use of hypnotics by elderly psychiatric patients taking zolpidem, estazolam, or flunitrazepam". Asia-Pacific Psychiatry. 7 (3): 298–305. doi:10.1111/appy.12147. PMID 25296384. S2CID 5782780.
  51. ^ Schmidt LG, Grohmann R, Müller-Oerlinghausen B, Otto M, Rüther E, Wolf B (June 1989). "Prevalence of benzodiazepine abuse and dependence in psychiatric in-patients with different nosology. An assessment of hospital-based drug surveillance data". The British Journal of Psychiatry. 154 (6): 839–843. doi:10.1192/bjp.154.6.839. PMID 2574611. S2CID 10441280.
  52. ^ Airagnes G, Lemogne C, Renuy A, Goldberg M, Hoertel N, Roquelaure Y, et al. (May 2019). "Prevalence of prescribed benzodiazepine long-term use in the French general population according to sociodemographic and clinical factors: findings from the CONSTANCES cohort". BMC Public Health. 19 (1): 566. doi:10.1186/s12889-019-6933-8. PMC 6518636. PMID 31088561.
  53. ^ Soyka M (June 2017). "Treatment of Benzodiazepine Dependence" (PDF). The New England Journal of Medicine. 376 (24): 2399–2400. doi:10.1056/NEJMc1705239. PMID 28614686.
  54. ^ HealthDay News (3 January 2019). "Prevalence of Benzodiazepine Use 12.6 Percent in the United States". Psychiatry Advisor. Haymarket.
  55. ^ Rastogi RB, Lapierre YD, Singhal RL (1978). "Some neurochemical correlates of "rebound" phenomenon observed during withdrawal after long-term exposure to 1, 4-benzodiazepines". Progress in Neuro-Psychopharmacology. 2 (1): 43–54. doi:10.1016/0364-7722(78)90021-8. PMID 31644.
  56. ^ Laux G (May 1979). "[A case of Lexotanil dependence. Case report on tranquilizer abuse]". Der Nervenarzt. 50 (5): 326–327. PMID 37451.
  57. ^ Fontaine R, Chouinard G, Annable L (July 1984). "Rebound anxiety in anxious patients after abrupt withdrawal of benzodiazepine treatment". The American Journal of Psychiatry. 141 (7): 848–852. doi:10.1176/ajp.141.7.848. PMID 6145363.
  58. ^ Chouinard G, Labonte A, Fontaine R, Annable L (1983). "New concepts in benzodiazepine therapy: rebound anxiety and new indications for the more potent benzodiazepines". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 7 (4–6): 669–673. doi:10.1016/0278-5846(83)90043-X. PMID 6141609. S2CID 32967696.
  59. ^ Böning J (May 1981). "[Bromazepam withdrawal delirium - a psychopharmacological contribution to clinical withdrawal syndromes (author's transl)]". Der Nervenarzt. 52 (5): 293–297. PMID 6113557.
  60. ^ Thomas P, Lebrun C, Chatel M (March 1993). "De novo absence status epilepticus as a benzodiazepine withdrawal syndrome". Epilepsia. 34 (2): 355–358. doi:10.1111/j.1528-1157.1993.tb02421.x. PMID 8384109. S2CID 45915803.
  61. ^ Fukuda M, Nakajima N, Tomita M (January 1999). "Generalized tonic-clonic seizures following withdrawal of therapeutic dose of bromazepam". Pharmacopsychiatry. 32 (1): 42–43. doi:10.1055/s-2007-979188. PMID 10071183. S2CID 260238907.
  62. ^ Agarwal RA, Lapierre YD, Rastogi RB, Singhal RL (May 1977). "Alterations in brain 5-hydroxytryptamine metabolism during the 'withdrawal' phase after chronic treatment with diazepam and bromazepam". British Journal of Pharmacology. 60 (1): 3–9. doi:10.1111/j.1476-5381.1977.tb16740.x. PMC 1667179. PMID 18243.
  63. ^ Professor Heather Ashton (2002). "Benzodiazepines: How They Work and How to Withdraw".
  64. ^ O'Connor RD (1993). "Benzodiazepine dependence--a treatment perspective and an advocacy for control". NIDA Research Monograph. 131: 266–269. PMID 8105385.
  65. ^ Gandolfi E, Andrade M (December 2006). "[Drug-related toxic events in the state of São Paulo, Brazil]" [Drug-related toxic events in the state of São Paulo, Brazil]. Revista de Saude Publica (in Portuguese). 40 (6): 1056–1064. doi:10.1590/s0034-89102006000700014. PMID 17173163.
  66. ^ Pasinato E, Franciosi A, De Vanna M (1983). "["Alpha pattern coma" after poisoning with flunitrazepam and bromazepam. Case description]". Minerva Psichiatrica. 24 (2): 69–74. PMID 6140613.
  67. ^ Marrache F, Mégarbane B, Pirnay S, Rhaoui A, Thuong M (October 2004). "Difficulties in assessing brain death in a case of benzodiazepine poisoning with persistent cerebral blood flow". Human & Experimental Toxicology. 23 (10): 503–505. Bibcode:2004HETox..23..503M. doi:10.1191/0960327104ht478cr. PMID 15553176. S2CID 19380042.
  68. ^ Löscher W, Rogawski MA (December 2012). "How theories evolved concerning the mechanism of action of barbiturates". Epilepsia. 53 (Suppl 8): 12–25. doi:10.1111/epi.12025. PMID 23205959. S2CID 4675696.
  69. ^ Koyama K, Shimazu Y, Kikuno T, Kaziwara H, Sekiguti H (January 2003). "[Pharmacokinetics of bromazepam in 57 patients with acute drug intoxication]" [Pharmacokinetics of bromazepam in 57 patients with acute drug intoxication]. Chudoku Kenkyu (in Japanese). 16 (1): 51–56. PMID 12712542.
  70. ^ Staikowsky F, Theil F, Candella S (July 2005). "[Trends in the pharmaceutical profile of intentional drug overdoses seen in the emergency room]" [Trends in the pharmaceutical profile of intentional drug overdoses seen in the emergency room]. Presse Médicale (in French). 34 (12): 842–846. doi:10.1016/s0755-4982(05)84060-6. PMID 16097205.
  71. ^ Bertini S, Buronfosse F, Pineau X, Berny P, Lorgue G (December 1995). "Benzodiazepine poisoning in companion animals". Veterinary and Human Toxicology. 37 (6): 559–562. PMID 8588297.
  72. ^ Authier N, Balayssac D, Sautereau M, Zangarelli A, Courty P, Somogyi AA, et al. (November 2009). "Benzodiazepine dependence: focus on withdrawal syndrome". Annales Pharmaceutiques Françaises. 67 (6): 408–413. doi:10.1016/j.pharma.2009.07.001. PMID 19900604.
  73. ^ a b Ochs HR, Greenblatt DJ, Friedman H, Burstein ES, Locniskar A, Harmatz JS, Shader RI (May 1987). "Bromazepam pharmacokinetics: influence of age, gender, oral contraceptives, cimetidine, and propranolol". Clinical Pharmacology and Therapeutics. 41 (5): 562–570. doi:10.1038/clpt.1987.72. PMID 2882883. S2CID 1099919.
  74. ^ Hobi V, Kielholz P, Dubach UC (October 1981). "[The effect of bromazepam on fitness to drive (author's transl)]" [The effect of bromazepam on fitness to drive]. Munchener Medizinische Wochenschrift (in German). 123 (42): 1585–1588. PMID 6118830.
  75. ^ Hoffman LaRoche Pharmaceuticals (3 April 2008). . Australia: roche-australia.com. Archived from the original (PDF) on 19 July 2008. Retrieved 16 December 2008.
  76. ^ Martens PR (June 1994). "A sudden infant death like syndrome possibly induced by a benzodiazepine in breast-feeding". European Journal of Emergency Medicine. 1 (2): 86–87. doi:10.1097/00063110-199406000-00008. PMID 9422145.
  77. ^ Perucca E, Gatti G, Spina E (September 1994). "Clinical pharmacokinetics of fluvoxamine". Clinical Pharmacokinetics. 27 (3): 175–190. doi:10.2165/00003088-199427030-00002. PMID 7988100. S2CID 22472247.
  78. ^ Woods JH (March 1984). "Progress report on the stimulant-depressant abuse liability evaluation project". NIDA Research Monograph. 49: 59–62. PMID 6148695.
  79. ^ Staub C, Lacalle H, Fryc O (May 1994). "[Presence of psychotropic drugs in the blood of drivers responsible for car accidents, and who consumed alcohol at the same time]" [Presence of psychotropic drugs in the blood of drivers responsible for car accidents, and who consumed alcohol at the same time]. Sozial- und Präventivmedizin (in French). 39 (3): 143–149. doi:10.1007/BF01299658. PMID 8048274. S2CID 19379856.
  80. ^ Brinkmann B, Fechner G, Püschel K (December 1984). "Identification of mechanical asphyxiation in cases of attempted masking of the homicide". Forensic Science International. 26 (4): 235–245. doi:10.1016/0379-0738(84)90028-8. PMID 6519613.
  81. ^ de Boisjolly JM, Rougé-Maillart C, Roy PM, Roussel B, Turcant A, Delhumeau A (August 2003). "[Chemical submission]" [Chemical submission]. Presse Médicale (in French). 32 (26): 1216–1218. PMID 14506459.
  82. ^ Djezzar S, Questel F, Burin E, Dally S (May 2009). "Chemical submission: results of 4-year French inquiry". International Journal of Legal Medicine. 123 (3): 213–219. doi:10.1007/s00414-008-0291-x. PMID 18925406. S2CID 23902799.
  83. ^ . non-benzodiazepines.org.uk. Archived from the original on 2008-12-08. Retrieved 2008-10-31.
  84. ^ List of psychotropic substances under international control December 5, 2005, at the Wayback Machine (PDF). International Narcotics Control Board.
  85. ^ Sanal (8 January 2012). "Synthesis Of Drugs: Laboratory Synthesis Of Bromazepam".

External links edit

  • Bromazepam drug information from Lexi-Comp. Includes dosage information and a comprehensive list of international brand names.
  • Inchem - Bromazepam

May 01, 2024
bromazepam, sold, under, many, brand, names, benzodiazepine, mainly, anti, anxiety, agent, with, similar, side, effects, diazepam, addition, being, used, treat, anxiety, panic, states, bromazepam, used, premedicant, prior, minor, surgery, typically, comes, dos. Bromazepam sold under many brand names is a benzodiazepine It is mainly an anti anxiety agent with similar side effects to diazepam In addition to being used to treat anxiety or panic states bromazepam may be used as a premedicant prior to minor surgery Bromazepam typically comes in doses of 3 mg and 6 mg tablets 4 BromazepamClinical dataTrade namesLexotan Lexotanil othersAHFS Drugs comMicromedex Detailed Consumer InformationAddictionliabilityHigh 1 Routes ofadministrationBy mouthATC codeN05BA08 WHO Legal statusLegal statusBR Class B1 Psychoactive drugs 2 CA Schedule IV DE Prescription only Anlage III for higher doses UK Class C US Schedule IVPharmacokinetic dataBioavailability84 Protein binding70 MetabolismLiver P450Metabolites3 hydroxybromazepamElimination half life12 20 hours avg 17hr 3 ExcretionUrine 69 as metabolites 1 IdentifiersIUPAC name 7 bromo 5 pyridin 2 yl 1H benzo e 1 4 diazepin 2 3H oneCAS Number1812 30 2 YPubChem CID2441DrugBankDB01558 YChemSpider2347 YUNIIX015L14V0OKEGGD01245 YChEBICHEBI 31302ChEMBLChEMBL277062 YCompTox Dashboard EPA DTXSID40171081ECHA InfoCard100 015 748Chemical and physical dataFormulaC 14H 10Br N 3OMolar mass316 158 g mol 13D model JSmol Interactive imageSMILES C1C O NC2 C C C C C2 Br C N1 C3 CC CC N3InChI InChI 1S C14H10BrN3O c15 9 4 5 11 10 7 9 14 17 8 13 19 18 11 12 3 1 2 6 16 12 h1 7H 8H2 H 18 19 YKey VMIYHDSEFNYJSL UHFFFAOYSA N Y verify It was patented in 1961 by Roche and approved for medical use in 1974 5 Contents 1 Medical uses 2 Pharmacology 2 1 Pharmacokinetics 3 Side effects 3 1 Frequency and seriousness of adverse effects 3 2 Tolerance dependence and withdrawal 3 3 Overdose 4 Contraindications 4 1 Special populations 5 Interactions 6 Society and culture 6 1 Drug misuse 6 2 Brand names 6 3 Legal status 6 4 Synthesis 7 See also 8 References 9 External linksMedical uses editMedical uses include treatment of severe anxiety 6 Despite certain side effects and the emergence of alternative products e g pregabalin benzodiazepine medication remains an effective way of reducing problematic symptoms and is typically deemed effective by patients 7 8 and medical professionals 9 10 11 Similarly to other intermediate acting depressants it may be used as hypnotic medication 12 or in order to mitigate withdrawal effects of alcohol consumption 13 14 15 Pharmacology edit nbsp 50 Pills of Lexotanil containing 6 mg of Bromazepam apiece as sold by Hoffmann La Roche in Germany Bromazepam is a classical benzodiazepine other classical benzodiazepines include diazepam clonazepam oxazepam lorazepam nitrazepam flurazepam and clorazepate 16 Its molecular structure is composed of a diazepine connected to a benzene ring and a pyridine ring the benzene ring having a single nitrogen atom that replaces one of the carbon atoms in the ring structure 17 It is a 1 4 benzodiazepine which means that the nitrogens on the seven sided diazepine ring are in the 1 and 4 positions Bromazepam binds to the GABA receptor GABAA causing a conformational change and increasing the inhibitory effects of GABA It acts as a positive modulator increasing the receptors response when activated by GABA itself or an agonist such as alcohol As opposed to barbital BZDs are not GABA receptor activators and rely on increasing the neurotransmitter s natural activity 18 Bromazepam is an intermediate acting benzodiazepine is moderately lipophilic compared to other substances of its class 19 and metabolised hepatically via oxidative pathways 20 It does not possess any antidepressant or antipsychotic qualities 21 After night time administration of bromazepam a highly significant reduction of gastric acid secretion occurs during sleep followed by a highly significant rebound in gastric acid production the following day 22 Bromazepam alters the electrical status of the brain causing an increase in beta activity and a decrease in alpha activity in EEG recordings 23 Pharmacokinetics edit Bromazepam is reported to be metabolized by a hepatic enzyme belonging to the Cytochrome P450 family of enzymes In 2003 a team led by Oda Manami at Oita Medical University reported that CYP3A4 a member of the Cytochrome P450 family was not the responsible enzyme since itraconazole a known inhibitor of CYP3A4 did not affect its metabolism 24 In 1995 J van Harten at the Solvay Pharmaceutical Department of Clinical Pharmacology in Weesp reported that fluvoxamine which is a potent inhibitor of CYP1A2 a less potent CYP3A4 inhibitor and a negligible inhibitor of CYP2D6 does inhibit its metabolism 25 The major metabolite of bromazepam is hydroxybromazepam 24 which is an active agent too and has a half life approximately equal to that of bromazepam citation needed Side effects editBromazepam is similar in side effects to other benzodiazepines The most common side effects reported are drowsiness sedation ataxia memory impairment and dizziness 26 Impairments to memory functions are common with bromazepam and include a reduced working memory and reduced ability to process environmental information 27 28 29 A 1975 experiment on healthy male college students exploring the effects of four different drugs on learning capacity observed that taking bromazepam alone at 6 mg 3 times daily for 2 weeks impaired learning capacities significantly In combination with alcohol impairments in learning capacity became even more pronounced 30 Various studies report impaired memory visual information processing and sensory data and impaired psychomotor performance 31 32 33 deterioration of cognition including attention capacity and impaired co ordinative skills 34 35 impaired reactive and attention performance which can impair driving skills 36 drowsiness and decrease in libido 37 38 Unsteadiness after taking bromazepam is however less pronounced than other benzodiazepines such as lorazepam 39 On occasion benzodiazepines can induce extreme alterations in memory such as anterograde amnesia and amnesic automatism which may have medico legal consequences Such reactions occur usually only at the higher dose end of the prescribing spectrum 40 Very rarely dystonia can develop 41 Up to 30 treated on a long term basis develop a form of dependence i e these patients cannot stop the medication without experiencing physical and or psychological benzodiazepine withdrawal symptoms Leukopenia and liver damage of the cholestatic type with or without jaundice icterus have additionally been seen the original manufacturer Roche recommends regular laboratory examinations to be performed routinely Ambulatory patients should be warned that bromazepam may impair the ability to drive vehicles and to operate machinery The impairment is worsened by consumption of alcohol because both act as central nervous system depressants During the course of therapy tolerance to the sedative effect usually develops Frequency and seriousness of adverse effects edit As with all medication the frequency and seriousness of side effects varies greatly depending on quantities consumed 42 43 In a study about bromazepam s negative effects on psychomotor skills and driving ability it was noted that 3 mg doses caused minimal impairment 44 It also appeared that impairment may be tied to methods of testing more so than on the product s intrinsic activity 45 Moreover side effects other than drowsiness dizziness and ataxia seem to be rare 46 and not experienced by more than a few percent of users The use of other comparable medication seems to display an identically moderate side effect profile 47 48 49 Tolerance dependence and withdrawal edit Prolonged use of bromazepam can cause tolerance and may lead to both physical and psychological dependence on the drug and as a result it is a medication which is controlled by international law It is nonetheless important to note that dependence long term use and misuse occur in a minority of cases 50 51 52 and are not representative of most patients experience with this type of medication 53 54 It shares with other benzodiazepines the risk of abuse misuse psychological dependence or physical dependence 55 56 A withdrawal study demonstrated both psychological dependence and physical dependence on bromazepam including marked rebound anxiety after 4 weeks chronic use Those whose dose was gradually reduced experienced no withdrawal 57 Patients treated with bromazepam for generalised anxiety disorder were found to experience withdrawal symptoms such as a worsening of anxiety as well as the development of physical withdrawal symptoms when abruptly withdrawn bromazepam 58 Abrupt or over rapid withdrawal from bromazepam after chronic use even at therapeutic prescribed doses can lead to a severe withdrawal syndrome including status epilepticus and a condition resembling delerium tremens 59 60 61 Animal studies have shown that chronic administration of diazepam or bromazepam causes a decrease in spontaneous locomotor activity decreased turnover of noradrenaline and dopamine and serotonin increased activity of tyrosine hydroxylase and increased levels of the catecholamines During withdrawal of bromazepam or diazepam a fall in tryptophan serotonin levels occurs as part of the benzodiazepine withdrawal syndrome 62 Changes in the levels of these chemicals in the brain can cause headaches anxiety tension depression insomnia restlessness confusion irritability sweating dysphoria dizziness derealization depersonalization numbness tingling of extremities hypersensitivity to light sound and smell perceptual distortions nausea vomiting diarrhea appetite loss hallucinations delirium seizures tremor stomach cramps myalgia agitation palpitations tachycardia panic attacks short term memory loss and hyperthermia 63 64 Overdose edit Main article Benzodiazepine overdose Bromazepam is commonly involved in drug overdoses 65 A severe bromazepam benzodiazepine overdose may result in an alpha pattern coma type 66 The toxicity of bromazepam in overdosage increases when combined with other CNS depressant drugs such as alcohol or sedative hypnotic drugs 67 Similarly to other benzodiazepines however being a positive modulator of certain neuroreceptors and not an agonist the product has reduced overdose potential compared to older products of the barbiturate class Its consumption alone is very seldom fatal in healthy adults 68 69 Bromazepam was in 2005 the most common benzodiazepine involved in intentional overdoses in France 70 Bromazepam has also been responsible for accidental poisonings in companion animals A review of benzodiazepine poisonings in cats and dogs from 1991 to 1994 found bromazepam to be responsible for significantly more poisonings than any other benzodiazepine 71 Contraindications editBenzodiazepines require special precaution if used in elderly pregnant child alcohol or drug dependent individuals and individuals with comorbid psychiatric disorders 72 Special populations edit Globally bromazepam is contraindicated and should be used with caution in women who are pregnant the elderly patients with a history of alcohol or other substance abuse disorders and children In 1987 a team of scientists led by Ochs reported that the elimination half life peak serum concentration and serum free fraction are significantly elevated and the oral clearance and volume of distribution significantly lowered in elderly subjects 73 The clinical consequence is that the elderly should be treated with lower doses than younger patients Bromazepam may affect driving and ability to operate machinery 74 Bromazepam is pregnancy category D a classification that means that bromazepam has been shown to cause harm to the unborn child The Hoffman LaRoche product information leaflet warns against breast feeding while taking bromazepam There has been at least one report of sudden infant death syndrome linked to breast feeding while consuming bromazepam 75 76 Interactions editCimetidine fluvoxamine and propranolol causes a marked increase in the elimination half life of bromazepam leading to increased accumulation of bromazepam 73 77 25 Society and culture editDrug misuse edit See also Benzodiazepine use disorder Bromazepam has a similar misuse risk as other benzodiazepines such as diazepam 78 In France car accidents involving psychotropic drugs in combination with alcohol itself a major contributor found benzodiazepines mainly diazepam nordiazepam and bromazepam to be the most common drug present in the blood stream almost twice that of the next most common drug cannabis 79 Bromazepam has also been used in serious criminal offences including robbery homicide and sexual assault 80 81 82 Brand names edit It is marketed under several brand names including Brozam Lectopam Lexomil Lexotan Lexilium Lexaurin Brazepam Rekotnil Bromaze Somalium Lexatin Calmepam Zepam and Lexotanil 83 Legal status edit Bromazepam is a Schedule IV drug under the Convention on Psychotropic Substances 84 Synthesis edit nbsp Bromazepam synthesis 85 See also editBenzodiazepine Benzodiazepine dependence Benzodiazepine withdrawal syndromeReferences edit a b Bromazepam Uses Interactions Mechanism of Action DrugBank Online Retrieved 2024 02 25 Anvisa 2023 03 31 RDC Nº 784 Listas de Substancias Entorpecentes Psicotropicas Precursoras e Outras sob Controle Especial Collegiate Board Resolution No 784 Lists of Narcotic Psychotropic Precursor and Other Substances under Special Control in Brazilian Portuguese Diario Oficial da Uniao published 2023 04 04 Archived from the original on 2023 08 03 Retrieved 2023 08 16 Lexotan bromazepam Product Insert PDF Roche 23 October 2012 Bromazepam Pharmaceutical Benefits Scheme PBS Australian Government Department of Health Retrieved 23 March 2014 Fischer J Ganellin CR 2006 Analogue based Drug Discovery John Wiley amp Sons p 53X ISBN 9783527607495 Content Not Available www uptodate com Retrieved 2017 09 07 Podiwinsky F Jellinger K March 1979 Bromazepam in the treatment of somatized psychogenic disorders author s transl Bromazepam in the treatment of somatized psychogenic disorders Wiener Klinische Wochenschrift in German 91 7 240 244 PMID 34934 Laxenaire M Kahn JP Marchand P May 1982 A clinical trial of bromazepam author s transl A clinical trial of bromazepam La Nouvelle Presse Medicale in French 11 22 1699 1701 PMID 6124936 Ropert R Bernes J Dachary JM 1987 Efficacy and tolerance of alprazolam and bromazepam in flexible doses Double blind study in 119 ambulatory anxious patients Efficacy and tolerance of alprazolam and bromazepam in flexible doses Double blind study in 119 ambulatory anxious patients L Encephale in French 13 2 89 95 PMID 2885173 Hallett C Dean BC 11 August 2008 Bromazepam acute benefit risk assessment in general practice Current Medical Research and Opinion 8 10 683 688 doi 10 1185 03007998409110117 PMID 6144455 Bromazepam PDF Haute Autorite de sante HAS in French 7 September 2016 Bromazepam Bromazepam Repertoire des Specialites Pharmaceutiques ANSM Agence Nationale de Securite du Medicament et des Produits de Sante French National Security Agency of Medicines and Health Products Chweh AY Lin YB Swinyard EA April 1984 Hypnotic action of benzodiazepines a possible mechanism Life Sciences 34 18 1763 1768 doi 10 1016 0024 3205 84 90576 9 PMID 6145073 Cordingley GJ Dean BC Hallett C 11 August 2008 A multi centre double blind parallel trial of bromazepam Lexotan and lorazepam to compare the acute benefit risk ratio in the treatment of patients with anxiety Current Medical Research and Opinion 9 7 505 510 doi 10 1185 03007998509109625 PMID 2863089 Braestrup C Squires RF April 1978 Pharmacological characterization of benzodiazepine receptors in the brain European Journal of Pharmacology 48 3 263 270 doi 10 1016 0014 2999 78 90085 7 PMID 639854 Bromazepam Eutimia com Salud Mental c 1999 2002 Poisbeau P Gazzo G Calvel L 11 September 2018 Anxiolytics targeting GABAA receptors Insights on etifoxine The World Journal of Biological Psychiatry 19 sup1 S36 S45 doi 10 1080 15622975 2018 1468030 PMID 30204559 Adeyemo MA Idowu SO 25 November 2016 Correlation of lipophilicity descriptors with pharmacokinetic parameters of selected benzodiazepines African Journal of Biomedical Research 19 3 213 218 Oelschlager H July 1989 Chemical and pharmacologic aspects of benzodiazepines Schweizerische Rundschau fur Medizin Praxis in German 78 27 28 766 772 PMID 2570451 Amphoux G Agussol P Girard J May 1982 The action of bromazepam on anxiety author s transl The action of bromazepam on anxiety La Nouvelle Presse Medicale in French 11 22 1738 1740 PMID 6124947 Stacher G Starker D February 1974 Inhibitory effect of bromazepam on basal and betazole stimulated gastric acid secretion in man Gut 15 2 116 120 doi 10 1136 gut 15 2 116 PMC 1412901 PMID 4820635 Fink M Weinfeld RE Schwartz MA Conney AH August 1976 Blood levels and electroencephalographic effects of diazepam and bromazepam Clinical Pharmacology and Therapeutics 20 2 184 191 doi 10 1002 cpt1976202184 PMID 7375 S2CID 38155674 a b Oda M Kotegawa T Tsutsumi K Ohtani Y Kuwatani K Nakano S November 2003 The effect of itraconazole on the pharmacokinetics and pharmacodynamics of bromazepam in healthy volunteers European Journal of Clinical Pharmacology 59 8 9 615 619 doi 10 1007 s00228 003 0681 4 PMID 14517708 S2CID 24131632 a b van Harten J 1995 Overview of the pharmacokinetics of fluvoxamine Clinical Pharmacokinetics 29 Suppl 1 1 9 doi 10 2165 00003088 199500291 00003 PMID 8846617 S2CID 71812133 LECTOPAM RxMed Retrieved 23 March 2014 Munte TF Gehde E Johannes S Seewald M Heinze HJ 1996 Effects of alprazolam and bromazepam on visual search and verbal recognition memory in humans a study with event related brain potentials Neuropsychobiology 34 1 49 56 doi 10 1159 000119291 PMID 8884760 Montenegro M Veiga H Deslandes A Cagy M McDowell K Pompeu F et al June 2005 Neuromodulatory effects of caffeine and bromazepam on visual event related potential P300 a comparative study Arquivos de Neuro Psiquiatria 63 2B 410 415 doi 10 1590 s0004 282x2005000300009 PMID 16059590 Cunha M Portela C Bastos VH Machado D Machado S Velasques B et al December 2008 Responsiveness of sensorimotor cortex during pharmacological intervention with bromazepam Neuroscience Letters 448 1 33 36 doi 10 1016 j neulet 2008 10 024 PMID 18938214 S2CID 22491979 Liljequist R Linnoila M Mattila MJ Saario I Seppala T October 1975 Effect of two weeks treatment with thioridazine chlorpromazine sulpiride and bromazepam alone or in combination with alcohol on learning and memory in man Psychopharmacologia 44 2 205 208 doi 10 1007 BF00421011 PMID 710 S2CID 36415883 Stacher G Bauer P Brunner H Grunberger J January 1976 Gastric acid secretion serum gastrin levels and psychomotor function under the influence of placebo insulin hypoglycemia and or bromazepam International Journal of Clinical Pharmacology and Biopharmacy 13 1 1 10 PMID 2560 Bourin M Auget JL Colombel MC Larousse C 1989 Effects of single oral doses of bromazepam buspirone and clobazam on performance tasks and memory Neuropsychobiology 22 3 141 145 doi 10 1159 000118609 PMID 2577220 Puga F Sampaio I Veiga H Ferreira C Cagy M Piedade R Ribeiro P December 2007 The effects of bromazepam on the early stage of visual information processing P100 Arquivos de Neuro Psiquiatria 65 4A 955 959 doi 10 1590 s0004 282x2007000600006 PMID 18094853 Saario I April 1976 Psychomotor skills during subacute treatment with thioridazine and bromazepam and their combined effects with alcohol Annals of Clinical Research 8 2 117 123 PMID 7178 Jansen AA Verbaten MN Slangen JL 1988 Acute effects of bromazepam on signal detection performance digit symbol substitution test and smooth pursuit eye movements Neuropsychobiology 20 2 91 95 doi 10 1159 000118481 PMID 2908134 Seppala T Saario I Mattila MJ 1976 Two Weeks Treatment with Chlorpromazine Thioridazine Sulpiride or Bromazepam Actions and Interactions with Alcohol on Psychomotor Skills Related to Driving Alcohol Drugs and Driving Modern Trends in Pharmacopsychiatry Vol 11 pp 85 90 doi 10 1159 000399456 ISBN 978 3 8055 2349 3 PMID 9581 Horseau C Brion S May 1982 Clinical trial of bromazepam Thirty four cases author s transl La Nouvelle Presse Medicale in French 11 22 1741 1743 PMID 6124948 Perret J Zagala A Gaio JM Hommel M Meaulle F Pellat J Pollak P May 1982 Bromazepam in anxiety Clinical evaluation author s transl La Nouvelle Presse Medicale in French 11 22 1722 1724 PMID 6124942 Patat A Foulhoux P July 1985 Effect on postural sway of various benzodiazepine tranquillizers British Journal of Clinical Pharmacology 20 1 9 16 doi 10 1111 j 1365 2125 1985 tb02792 x PMC 1400619 PMID 2862898 Rager P Benezech M January 1986 Memory gaps and hypercomplex automatisms after a single oral dose of benzodiazepines clinical and medico legal aspects Memory gaps and hypercomplex automatisms after a single oral dose of benzodiazepines clinical and medico legal aspects Annales Medico Psychologiques in French 144 1 102 109 PMID 2876672 Perez Trullen JM Modrego Pardo PJ Vazquez Andre M Lopez Lozano JJ January 1992 Bromazepam induced dystonia Biomedicine amp Pharmacotherapy 46 8 375 376 doi 10 1016 0753 3322 92 90306 r PMID 1292648 LEXOMIL Bromazepam Posologie Effets secondaires Grossesse How to Manage Common Drug Side Effects Hobi V Dubach UC Skreta M Forgo I Riggenbach H 25 June 2016 The subacute effect of bromazepam on psychomotor activity and subjective mood The Journal of International Medical Research 10 3 140 146 doi 10 1177 030006058201000302 PMID 6124470 S2CID 25165191 Hobi V Dubach UC Skreta M Forgo J Riggenbach H 25 June 2016 The effect of bromazepam on psychomotor activity and subjective mood The Journal of International Medical Research 9 2 89 97 doi 10 1177 030006058100900201 PMID 6112173 S2CID 21899896 Side effect information for Bromazepam Side effect information for Lorazepam Side effect information for Diazepam Notice patient LORAZEPAM MYLAN 1 mg comprime pellicule secable Base de donnees publique des medicaments Yen CF Ko CH Chang YP Yu CY Huang MF Yeh YC et al September 2015 Dependence misuse and beliefs regarding use of hypnotics by elderly psychiatric patients taking zolpidem estazolam or flunitrazepam Asia Pacific Psychiatry 7 3 298 305 doi 10 1111 appy 12147 PMID 25296384 S2CID 5782780 Schmidt LG Grohmann R Muller Oerlinghausen B Otto M Ruther E Wolf B June 1989 Prevalence of benzodiazepine abuse and dependence in psychiatric in patients with different nosology An assessment of hospital based drug surveillance data The British Journal of Psychiatry 154 6 839 843 doi 10 1192 bjp 154 6 839 PMID 2574611 S2CID 10441280 Airagnes G Lemogne C Renuy A Goldberg M Hoertel N Roquelaure Y et al May 2019 Prevalence of prescribed benzodiazepine long term use in the French general population according to sociodemographic and clinical factors findings from the CONSTANCES cohort BMC Public Health 19 1 566 doi 10 1186 s12889 019 6933 8 PMC 6518636 PMID 31088561 Soyka M June 2017 Treatment of Benzodiazepine Dependence PDF The New England Journal of Medicine 376 24 2399 2400 doi 10 1056 NEJMc1705239 PMID 28614686 HealthDay News 3 January 2019 Prevalence of Benzodiazepine Use 12 6 Percent in the United States Psychiatry Advisor Haymarket Rastogi RB Lapierre YD Singhal RL 1978 Some neurochemical correlates of rebound phenomenon observed during withdrawal after long term exposure to 1 4 benzodiazepines Progress in Neuro Psychopharmacology 2 1 43 54 doi 10 1016 0364 7722 78 90021 8 PMID 31644 Laux G May 1979 A case of Lexotanil dependence Case report on tranquilizer abuse Der Nervenarzt 50 5 326 327 PMID 37451 Fontaine R Chouinard G Annable L July 1984 Rebound anxiety in anxious patients after abrupt withdrawal of benzodiazepine treatment The American Journal of Psychiatry 141 7 848 852 doi 10 1176 ajp 141 7 848 PMID 6145363 Chouinard G Labonte A Fontaine R Annable L 1983 New concepts in benzodiazepine therapy rebound anxiety and new indications for the more potent benzodiazepines Progress in Neuro Psychopharmacology amp Biological Psychiatry 7 4 6 669 673 doi 10 1016 0278 5846 83 90043 X PMID 6141609 S2CID 32967696 Boning J May 1981 Bromazepam withdrawal delirium a psychopharmacological contribution to clinical withdrawal syndromes author s transl Der Nervenarzt 52 5 293 297 PMID 6113557 Thomas P Lebrun C Chatel M March 1993 De novo absence status epilepticus as a benzodiazepine withdrawal syndrome Epilepsia 34 2 355 358 doi 10 1111 j 1528 1157 1993 tb02421 x PMID 8384109 S2CID 45915803 Fukuda M Nakajima N Tomita M January 1999 Generalized tonic clonic seizures following withdrawal of therapeutic dose of bromazepam Pharmacopsychiatry 32 1 42 43 doi 10 1055 s 2007 979188 PMID 10071183 S2CID 260238907 Agarwal RA Lapierre YD Rastogi RB Singhal RL May 1977 Alterations in brain 5 hydroxytryptamine metabolism during the withdrawal phase after chronic treatment with diazepam and bromazepam British Journal of Pharmacology 60 1 3 9 doi 10 1111 j 1476 5381 1977 tb16740 x PMC 1667179 PMID 18243 Professor Heather Ashton 2002 Benzodiazepines How They Work and How to Withdraw O Connor RD 1993 Benzodiazepine dependence a treatment perspective and an advocacy for control NIDA Research Monograph 131 266 269 PMID 8105385 Gandolfi E Andrade M December 2006 Drug related toxic events in the state of Sao Paulo Brazil Drug related toxic events in the state of Sao Paulo Brazil Revista de Saude Publica in Portuguese 40 6 1056 1064 doi 10 1590 s0034 89102006000700014 PMID 17173163 Pasinato E Franciosi A De Vanna M 1983 Alpha pattern coma after poisoning with flunitrazepam and bromazepam Case description Minerva Psichiatrica 24 2 69 74 PMID 6140613 Marrache F Megarbane B Pirnay S Rhaoui A Thuong M October 2004 Difficulties in assessing brain death in a case of benzodiazepine poisoning with persistent cerebral blood flow Human amp Experimental Toxicology 23 10 503 505 Bibcode 2004HETox 23 503M doi 10 1191 0960327104ht478cr PMID 15553176 S2CID 19380042 Loscher W Rogawski MA December 2012 How theories evolved concerning the mechanism of action of barbiturates Epilepsia 53 Suppl 8 12 25 doi 10 1111 epi 12025 PMID 23205959 S2CID 4675696 Koyama K Shimazu Y Kikuno T Kaziwara H Sekiguti H January 2003 Pharmacokinetics of bromazepam in 57 patients with acute drug intoxication Pharmacokinetics of bromazepam in 57 patients with acute drug intoxication Chudoku Kenkyu in Japanese 16 1 51 56 PMID 12712542 Staikowsky F Theil F Candella S July 2005 Trends in the pharmaceutical profile of intentional drug overdoses seen in the emergency room Trends in the pharmaceutical profile of intentional drug overdoses seen in the emergency room Presse Medicale in French 34 12 842 846 doi 10 1016 s0755 4982 05 84060 6 PMID 16097205 Bertini S Buronfosse F Pineau X Berny P Lorgue G December 1995 Benzodiazepine poisoning in companion animals Veterinary and Human Toxicology 37 6 559 562 PMID 8588297 Authier N Balayssac D Sautereau M Zangarelli A Courty P Somogyi AA et al November 2009 Benzodiazepine dependence focus on withdrawal syndrome Annales Pharmaceutiques Francaises 67 6 408 413 doi 10 1016 j pharma 2009 07 001 PMID 19900604 a b Ochs HR Greenblatt DJ Friedman H Burstein ES Locniskar A Harmatz JS Shader RI May 1987 Bromazepam pharmacokinetics influence of age gender oral contraceptives cimetidine and propranolol Clinical Pharmacology and Therapeutics 41 5 562 570 doi 10 1038 clpt 1987 72 PMID 2882883 S2CID 1099919 Hobi V Kielholz P Dubach UC October 1981 The effect of bromazepam on fitness to drive author s transl The effect of bromazepam on fitness to drive Munchener Medizinische Wochenschrift in German 123 42 1585 1588 PMID 6118830 Hoffman LaRoche Pharmaceuticals 3 April 2008 NAME OF THE MEDICINE LEXOTAN Australia roche australia com Archived from the original PDF on 19 July 2008 Retrieved 16 December 2008 Martens PR June 1994 A sudden infant death like syndrome possibly induced by a benzodiazepine in breast feeding European Journal of Emergency Medicine 1 2 86 87 doi 10 1097 00063110 199406000 00008 PMID 9422145 Perucca E Gatti G Spina E September 1994 Clinical pharmacokinetics of fluvoxamine Clinical Pharmacokinetics 27 3 175 190 doi 10 2165 00003088 199427030 00002 PMID 7988100 S2CID 22472247 Woods JH March 1984 Progress report on the stimulant depressant abuse liability evaluation project NIDA Research Monograph 49 59 62 PMID 6148695 Staub C Lacalle H Fryc O May 1994 Presence of psychotropic drugs in the blood of drivers responsible for car accidents and who consumed alcohol at the same time Presence of psychotropic drugs in the blood of drivers responsible for car accidents and who consumed alcohol at the same time Sozial und Praventivmedizin in French 39 3 143 149 doi 10 1007 BF01299658 PMID 8048274 S2CID 19379856 Brinkmann B Fechner G Puschel K December 1984 Identification of mechanical asphyxiation in cases of attempted masking of the homicide Forensic Science International 26 4 235 245 doi 10 1016 0379 0738 84 90028 8 PMID 6519613 de Boisjolly JM Rouge Maillart C Roy PM Roussel B Turcant A Delhumeau A August 2003 Chemical submission Chemical submission Presse Medicale in French 32 26 1216 1218 PMID 14506459 Djezzar S Questel F Burin E Dally S May 2009 Chemical submission results of 4 year French inquiry International Journal of Legal Medicine 123 3 213 219 doi 10 1007 s00414 008 0291 x PMID 18925406 S2CID 23902799 Benzodiazepine Names non benzodiazepines org uk Archived from the original on 2008 12 08 Retrieved 2008 10 31 List of psychotropic substances under international control Archived December 5 2005 at the Wayback Machine PDF International Narcotics Control Board Sanal 8 January 2012 Synthesis Of Drugs Laboratory Synthesis Of Bromazepam External links editBromazepam drug information from Lexi Comp Includes dosage information and a comprehensive list of international brand names Inchem Bromazepam Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Bromazepam amp oldid 1210642919, wikipedia, wiki, book, books, library,

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