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Wikipedia

Quazepam

January 31, 2023

Quazepam, sold under brand name Doral among others, is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s.[1] Quazepam is used for the treatment of insomnia including sleep induction and sleep maintenance.[2] Quazepam induces impairment of motor function and has relatively (and uniquely) selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines (due to its novel receptor-subtype selectively).[3][4] Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.[5]

Quazepam
Clinical data
Trade namesDoral
AHFS/Drugs.comConsumer Drug Information
MedlinePlusa684001
Pregnancy
category
  • AU: D
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability29–35%
MetabolismLiver
Elimination half-life39 hours
ExcretionKidney
Identifiers
  • 7-chloro-5-(2-fluorophenyl)-1-(2,2,2-trifluoroethyl)-3H-1,4-benzodiazepine-2-thione
CAS Number
  • 36735-22-5 Y
PubChem CID
  • 4999
IUPHAR/BPS
  • 7288
DrugBank
  • DB01589 Y
ChemSpider
  • 4825 Y
UNII
  • JF8V0828ZI
KEGG
  • D00457 Y
ChEMBL
  • ChEMBL1200472 N
CompTox Dashboard (EPA)
  • DTXSID60190193
ECHA InfoCard100.048.329
Chemical and physical data
FormulaC17H11ClF4N2S
Molar mass386.79 g·mol−1
3D model (JSmol)
  • Interactive image
  • FC(F)(F)CN1C(=S)C/N=C(\c2cc(Cl)ccc12)c3ccccc3F
  • InChI=1S/C17H11ClF4N2S/c18-10-5-6-14-12(7-10)16(11-3-1-2-4-13(11)19)23-8-15(25)24(14)9-17(20,21)22/h1-7H,8-9H2 Y
  • Key:IKMPWMZBZSAONZ-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

It was patented in 1970 and came into medical use in 1985.[6]

Medical uses

Quazepam is used for short-term treatment of insomnia related to sleep induction or sleep maintenance problems and has demonstrated superiority over other benzodiazepines such as temazepam. It had a fewer incidence of side effects than temazepam, including less sedation, amnesia, and less motor-impairment.[7][8][9][10] Usual dosage is 7.5 to 15 mg orally at bedtime.[11]

Quazepam is effective as a premedication prior to surgery.[12]

Side effects

Quazepam has fewer side effects than other benzodiazepines and less potential to induce tolerance and rebound effects.[13][14] There is significantly less potential for quazepam to induce respiratory depression or to adversely affect motor coordination than other benzodiazepines.[15] The different side effect profile of quazepam may be due to its more selective binding profile to type 1 benzodiazepine receptors.[16][17]

In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.[22]

Tolerance and dependence

Tolerance may occur to quazepam but more slowly than seen with other benzodiazepines such as triazolam.[23] Quazepam causes significantly less drug tolerance and less withdrawal symptoms including less rebound insomnia upon discontinuation compared to other benzodiazepines.[24][25][26][27] Quazepam may cause less rebound effects than other type1 benzodiazepine receptor selective nonbenzodiazepine drugs due to its longer half-life.[28] Short-acting hypnotics often cause next day rebound anxiety. Quazepam due to its pharmacological profile does not cause next day rebound withdrawal effects during treatment.[29]

No firm conclusions can be drawn, however, whether long-term use of quazepam does not produce tolerance as few, if any, long-term clinical trials extending beyond 4 weeks of chronic use have been conducted.[30] Quazepam should be withdrawn gradually if used beyond 4 weeks of use to avoid the risk of a severe benzodiazepine withdrawal syndrome developing. Very high dosage administration over prolonged periods of time, up to 52 weeks, of quazepam in animal studies provoked severe withdrawal symptoms upon abrupt discontinuation, including excitability, hyperactivity, convulsions and the death of two of the monkeys due to withdrawal-related convulsions. More monkeys died however, in the diazepam-treated monkeys.[31] In addition it has now been documented in the medical literature that one of the major metabolites of quazepam, N-desalkyl-2-oxoquazepam (N-desalkylflurazepam), which is long-acting and prone to accumulation, binds unselectively to benzodiazepine receptors, thus quazepam may not differ all that much pharmacologically from other benzodiazepines.[32]

Special precautions

Benzodiazepines require special precaution if used in the during pregnancy, in children, alcohol or drug-dependent individuals and individuals with comorbid psychiatric disorders.[33]

Quazepam and its active metabolites are excreted into breast milk.[34]

Accumulation of one of the active metabolites of quazepam, N-desalkylflurazepam, may occur in the elderly. A lower dose may be required in the elderly.[35]

Elderly

Quazepam is more tolerable for elderly patients compared to flurazepam due to its reduced next day impairments.[36] However, another study showed marked next day impairments after repeated administration due to accumulation of quazepam and its long-acting metabolites. Thus the medical literature shows conflicts on quazepam's side effect profile.[37] A further study showed significant balance impairments combined with an unstable posture after administration of quazepam in test subjects.[38] An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including quazepam, the nonbenzodiazepine sedative/hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative/hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.[39]

Interactions

The absorption rate is likely to be significantly reduced if quazepam is taken in the fasted state reducing the hypnotic effect of quazepam. If 3 or more hours have passed since eating food then some food should be eaten before taking quazepam.[40][41]

Pharmacology

Quazepam is a trifluoroalkyl type of benzodiazepine. Quazepam is unique amongst benzodiazepines in that it selectively targets the GABAA α1 subunit receptors which are responsible for inducing sleep. Its mechanism of action is very similar to zolpidem and zaleplon in its pharmacology and can successfully substitute for zolpidem and zaleplon in animal studies.[42][43][44]

Quazepam is selective for type I benzodiazepine receptors containing the α1 subunit, similar to other drugs such as zaleplon and zolpidem. As a result, quazepam has little or no muscle relaxant properties. Most other benzodiazepines are unselective and bind to type1 GABAA receptors and type2 GABAA receptors. Type1 GABAA receptors include the α1 subunit containing GABAA receptors which are responsible for hypnotic properties of the drug. Type 2 receptors include the α2, α3 and α5 subunits which are responsible for anxiolytic action, amnesia and muscle relaxant properties.[45][46] Thus quazepam may have less side effects than other benzodiazepines but, it has a very long half-life of 25 hours which reduces its benefits as a hypnotic due to likely next day sedation. It also has two active metabolites with half-lives of 28 and 79 hours. Quazepam may also cause less drug tolerance than other benzodiazepines such as temazepam and triazolam perhaps due to its subtype selectivity.[47][48][49][50] The longer half-life of quazepam may have the advantage however, of causing less rebound insomnia than shorter acting subtype selective nonbenzodiazepines.[8][28] However, one of the major metabolites of quazepam, the N-desmethyl-2-oxoquazepam (aka N-desalkylflurazepam), binds unselectively to both type1 and type2 GABAA receptors. The N-desmethyl-2-oxoquazepam metabolite also has a very long half-life and likely contributes to the pharmacological effects of quazepam.[51]

Pharmacokinetics

 
2-Oxoquazepam, a major active quazepam metabolite.

Quazepam has an absorption half-life of 0.4 hours with a peak in plasma levels after 1.75 hours. It is eliminated both renally and through feces.[52] The active metabolites of quazepam are 2-oxoquazepam and N-desalkyl-2-oxoquazepam. The N-desalkyl-2-oxoquazepam metabolite has only limited pharmacological activity compared to the parent compound quazepam and the active metabolite 2-oxoquazepam.[citation needed] Quazepam and its major active metabolite 2-oxoquazepam both show high selectivity for the type1 GABAA receptors.[53][54][55][56] The elimination half-life range of quazepam is between 27 and 41 hours.[30]

Mechanism of action

Quazepam modulates specific GABAA receptors via the benzodiazepine site on the GABAA receptor. This modulation enhances the actions of GABA, causing an increase in opening frequency of the chloride ion channel which results in an increased influx of chloride ions into the GABAA receptors. Quazepam, unique amongst benzodiazepine drugs selectively targets type1 benzodiazepine receptors which results reduced sleep latency in promotion of sleep.[57][58][59] Quazepam also has some anticonvulsant properties.[60]

EEG and sleep

Quazepam has potent sleep inducing and sleep maintaining properties.[61][62] Studies in both animals and humans have demonstrated that EEG changes induced by quazepam resemble normal sleep patterns whereas other benzodiazepines disrupt normal sleep. Quazepam promotes slow wave sleep.[63][64] This positive effect of quazepam on sleep architecture may be due to its high selectivity for type1 benzodiazepine receptors as demonstrated in animal and human studies. This makes quazepam unique in the benzodiazepine family of drugs.[65][66]

Drug misuse

See also: Benzodiazepine drug misuse

Quazepam is a drug with the potential for misuse. Two types of drug misuse can occur, either recreational misuse where the drug is taken to achieve a high, or when the drug is continued long term against medical advice.[67]

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  63. ^ Mariotti M, Ongini E (August 1983). "Differential effects of benzodiazepines on EEG activity and hypnogenic mechanisms of the brain stem in cats". Arch Int Pharmacodyn Ther. 264 (2): 203–19. PMID 6139096.
  64. ^ Kawasaki H, Urabe M, Nuki C, Yamamoto R, Takasaki K, Ohno H (October 1987). "[Electroencephalographic study of Sch 161 (quazepam), a new benzodiazepine hypnotic, in rats and rabbits]". Nippon Yakurigaku Zasshi (in Japanese). 90 (4): 221–38. doi:10.1254/fpj.90.221. PMID 3428780.
  65. ^ Sieghart W (July 1983). "Several new benzodiazepines selectively interact with a benzodiazepine receptor subtype". Neurosci. Lett. 38 (1): 73–8. doi:10.1016/0304-3940(83)90113-1. PMID 6136944. S2CID 42856742.
  66. ^ Wamsley JK, Golden JS, Yamamura HI, Barnett A (1985). "Quazepam, a sedative-hypnotic selective for the benzodiazepine type 1 receptor: autoradiographic localization in rat and human brain". Clin Neuropharmacol. 8. Suppl 1: S26–40. doi:10.1097/00002826-198508001-00005. PMID 2874881. S2CID 10557339.
  67. ^ Griffiths RR, Johnson MW (2005). "Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds". J Clin Psychiatry. 66. Suppl 9: 31–41. PMID 16336040.

External links

  • "Quazepam". Drug Information Portal. U.S. National Library of Medicine.

January 31, 2023
quazepam, sold, under, brand, name, doral, among, others, relatively, long, acting, benzodiazepine, derivative, drug, developed, schering, corporation, 1970s, used, treatment, insomnia, including, sleep, induction, sleep, maintenance, induces, impairment, moto. Quazepam sold under brand name Doral among others is a relatively long acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s 1 Quazepam is used for the treatment of insomnia including sleep induction and sleep maintenance 2 Quazepam induces impairment of motor function and has relatively and uniquely selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines due to its novel receptor subtype selectively 3 4 Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture 5 QuazepamClinical dataTrade namesDoralAHFS Drugs comConsumer Drug InformationMedlinePlusa684001PregnancycategoryAU DRoutes ofadministrationBy mouthATC codeN05CD10 WHO Legal statusLegal statusCA Schedule IV US Schedule IVPharmacokinetic dataBioavailability29 35 MetabolismLiverElimination half life39 hoursExcretionKidneyIdentifiersIUPAC name 7 chloro 5 2 fluorophenyl 1 2 2 2 trifluoroethyl 3H 1 4 benzodiazepine 2 thioneCAS Number36735 22 5 YPubChem CID4999IUPHAR BPS7288DrugBankDB01589 YChemSpider4825 YUNIIJF8V0828ZIKEGGD00457 YChEMBLChEMBL1200472 NCompTox Dashboard EPA DTXSID60190193ECHA InfoCard100 048 329Chemical and physical dataFormulaC 17H 11Cl F 4N 2SMolar mass386 79 g mol 13D model JSmol Interactive imageSMILES FC F F CN1C S C N C c2cc Cl ccc12 c3ccccc3FInChI InChI 1S C17H11ClF4N2S c18 10 5 6 14 12 7 10 16 11 3 1 2 4 13 11 19 23 8 15 25 24 14 9 17 20 21 22 h1 7H 8 9H2 YKey IKMPWMZBZSAONZ UHFFFAOYSA N Y N Y what is this verify It was patented in 1970 and came into medical use in 1985 6 Contents 1 Medical uses 2 Side effects 2 1 Tolerance and dependence 2 2 Special precautions 2 3 Elderly 3 Interactions 4 Pharmacology 5 Pharmacokinetics 6 Mechanism of action 7 EEG and sleep 8 Drug misuse 9 References 10 External linksMedical uses EditQuazepam is used for short term treatment of insomnia related to sleep induction or sleep maintenance problems and has demonstrated superiority over other benzodiazepines such as temazepam It had a fewer incidence of side effects than temazepam including less sedation amnesia and less motor impairment 7 8 9 10 Usual dosage is 7 5 to 15 mg orally at bedtime 11 Quazepam is effective as a premedication prior to surgery 12 Side effects EditQuazepam has fewer side effects than other benzodiazepines and less potential to induce tolerance and rebound effects 13 14 There is significantly less potential for quazepam to induce respiratory depression or to adversely affect motor coordination than other benzodiazepines 15 The different side effect profile of quazepam may be due to its more selective binding profile to type 1 benzodiazepine receptors 16 17 Ataxia 18 Daytime somnolence 19 Hypokinesia 20 Cognitive and performance impairments 21 In September 2020 the U S Food and Drug Administration FDA required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse misuse addiction physical dependence and withdrawal reactions consistently across all the medicines in the class 22 Tolerance and dependence Edit Tolerance may occur to quazepam but more slowly than seen with other benzodiazepines such as triazolam 23 Quazepam causes significantly less drug tolerance and less withdrawal symptoms including less rebound insomnia upon discontinuation compared to other benzodiazepines 24 25 26 27 Quazepam may cause less rebound effects than other type1 benzodiazepine receptor selective nonbenzodiazepine drugs due to its longer half life 28 Short acting hypnotics often cause next day rebound anxiety Quazepam due to its pharmacological profile does not cause next day rebound withdrawal effects during treatment 29 No firm conclusions can be drawn however whether long term use of quazepam does not produce tolerance as few if any long term clinical trials extending beyond 4 weeks of chronic use have been conducted 30 Quazepam should be withdrawn gradually if used beyond 4 weeks of use to avoid the risk of a severe benzodiazepine withdrawal syndrome developing Very high dosage administration over prolonged periods of time up to 52 weeks of quazepam in animal studies provoked severe withdrawal symptoms upon abrupt discontinuation including excitability hyperactivity convulsions and the death of two of the monkeys due to withdrawal related convulsions More monkeys died however in the diazepam treated monkeys 31 In addition it has now been documented in the medical literature that one of the major metabolites of quazepam N desalkyl 2 oxoquazepam N desalkylflurazepam which is long acting and prone to accumulation binds unselectively to benzodiazepine receptors thus quazepam may not differ all that much pharmacologically from other benzodiazepines 32 Special precautions Edit Benzodiazepines require special precaution if used in the during pregnancy in children alcohol or drug dependent individuals and individuals with comorbid psychiatric disorders 33 Quazepam and its active metabolites are excreted into breast milk 34 Accumulation of one of the active metabolites of quazepam N desalkylflurazepam may occur in the elderly A lower dose may be required in the elderly 35 Elderly Edit Quazepam is more tolerable for elderly patients compared to flurazepam due to its reduced next day impairments 36 However another study showed marked next day impairments after repeated administration due to accumulation of quazepam and its long acting metabolites Thus the medical literature shows conflicts on quazepam s side effect profile 37 A further study showed significant balance impairments combined with an unstable posture after administration of quazepam in test subjects 38 An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non drug treatments for insomnia in adults of all ages and that these interventions are underutilized Compared with the benzodiazepines including quazepam the nonbenzodiazepine sedative hypnotics appeared to offer few if any significant clinical advantages in efficacy or tolerability in elderly persons It was found that newer agents with novel mechanisms of action and improved safety profiles such as the melatonin agonists hold promise for the management of chronic insomnia in elderly people Long term use of sedative hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment anterograde amnesia daytime sedation motor incoordination and increased risk of motor vehicle accidents and falls In addition the effectiveness and safety of long term use of these agents remain to be determined It was concluded that more research is needed to evaluate the long term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia 39 Interactions EditThe absorption rate is likely to be significantly reduced if quazepam is taken in the fasted state reducing the hypnotic effect of quazepam If 3 or more hours have passed since eating food then some food should be eaten before taking quazepam 40 41 Pharmacology EditQuazepam is a trifluoroalkyl type of benzodiazepine Quazepam is unique amongst benzodiazepines in that it selectively targets the GABAA a1 subunit receptors which are responsible for inducing sleep Its mechanism of action is very similar to zolpidem and zaleplon in its pharmacology and can successfully substitute for zolpidem and zaleplon in animal studies 42 43 44 Quazepam is selective for type I benzodiazepine receptors containing the a1 subunit similar to other drugs such as zaleplon and zolpidem As a result quazepam has little or no muscle relaxant properties Most other benzodiazepines are unselective and bind to type1 GABAA receptors and type2 GABAA receptors Type1 GABAA receptors include the a1 subunit containing GABAA receptors which are responsible for hypnotic properties of the drug Type 2 receptors include the a2 a3 and a5 subunits which are responsible for anxiolytic action amnesia and muscle relaxant properties 45 46 Thus quazepam may have less side effects than other benzodiazepines but it has a very long half life of 25 hours which reduces its benefits as a hypnotic due to likely next day sedation It also has two active metabolites with half lives of 28 and 79 hours Quazepam may also cause less drug tolerance than other benzodiazepines such as temazepam and triazolam perhaps due to its subtype selectivity 47 48 49 50 The longer half life of quazepam may have the advantage however of causing less rebound insomnia than shorter acting subtype selective nonbenzodiazepines 8 28 However one of the major metabolites of quazepam the N desmethyl 2 oxoquazepam aka N desalkylflurazepam binds unselectively to both type1 and type2 GABAA receptors The N desmethyl 2 oxoquazepam metabolite also has a very long half life and likely contributes to the pharmacological effects of quazepam 51 Pharmacokinetics Edit 2 Oxoquazepam a major active quazepam metabolite Quazepam has an absorption half life of 0 4 hours with a peak in plasma levels after 1 75 hours It is eliminated both renally and through feces 52 The active metabolites of quazepam are 2 oxoquazepam and N desalkyl 2 oxoquazepam The N desalkyl 2 oxoquazepam metabolite has only limited pharmacological activity compared to the parent compound quazepam and the active metabolite 2 oxoquazepam citation needed Quazepam and its major active metabolite 2 oxoquazepam both show high selectivity for the type1 GABAA receptors 53 54 55 56 The elimination half life range of quazepam is between 27 and 41 hours 30 Mechanism of action EditQuazepam modulates specific GABAA receptors via the benzodiazepine site on the GABAA receptor This modulation enhances the actions of GABA causing an increase in opening frequency of the chloride ion channel which results in an increased influx of chloride ions into the GABAA receptors Quazepam unique amongst benzodiazepine drugs selectively targets type1 benzodiazepine receptors which results reduced sleep latency in promotion of sleep 57 58 59 Quazepam also has some anticonvulsant properties 60 EEG and sleep EditQuazepam has potent sleep inducing and sleep maintaining properties 61 62 Studies in both animals and humans have demonstrated that EEG changes induced by quazepam resemble normal sleep patterns whereas other benzodiazepines disrupt normal sleep Quazepam promotes slow wave sleep 63 64 This positive effect of quazepam on sleep architecture may be due to its high selectivity for type1 benzodiazepine receptors as demonstrated in animal and human studies This makes quazepam unique in the benzodiazepine family of drugs 65 66 Drug misuse EditSee also Benzodiazepine drug misuse Quazepam is a drug with the potential for misuse Two types of drug misuse can occur either recreational misuse where the drug is taken to achieve a high or when the drug is continued long term against medical advice 67 References Edit US Patent 3845039 Mendels J February 1994 Evaluation of the safety and efficacy of quazepam for the treatment of insomnia in psychiatric outpatients J Clin Psychiatry 55 2 60 5 PMID 7915708 Yasui M Kato A Kanemasa T Murata S Nishitomi K Koike K Tai N Shinohara S Tokomura M Horiuchi M Abe K June 2005 Pharmacological profiles of benzodiazepinergic hypnotics and correlations with receptor subtypes Nihon Shinkei Seishin Yakurigaku Zasshi Japanese Journal of Psychopharmacology 25 3 143 51 PMID 16045197 Ongini E Parravicini L Bamonte F Guzzon V Iorio LC Barnett A 1982 Pharmacological studies with quazepam a new benzodiazepine hypnotic Arzneimittelforschung 32 11 1456 62 PMID 6129857 Roth T Tietz EI Kramer M Kaffeman M 1979 The effect of a single dose of quazepam Sch 16134 on the sleep of chronic insomniacs J Int Med Res 7 6 583 7 doi 10 1177 030006057900700620 PMID 42593 S2CID 36725411 Fischer Jnos Ganellin C Robin 2006 Analogue based Drug Discovery John Wiley amp Sons p 538 ISBN 9783527607495 Tsoi WF March 1991 Insomnia drug treatment Ann Acad Med Singap 20 2 269 72 PMID 1679317 a b Kales A Bixler EO Soldatos CR Vela Bueno A Jacoby JA Kales JD March 1986 Quazepam and temazepam effects of short and intermediate term use and withdrawal Clin Pharmacol Ther 39 3 345 52 doi 10 1038 clpt 1986 51 PMID 2868823 S2CID 23792142 Hernandez Lara R Del Rosal PL Ponce MC 1983 Short term study of quazepam 15 milligrams in the treatment of insomnia J Int Med Res 11 3 162 6 doi 10 1177 030006058301100306 PMID 6347748 S2CID 35177500 Caldwell JR 1982 Short term quazepam treatment of insomnia in geriatric patients Pharmatherapeutica 3 4 278 82 PMID 6128741 Kales A Scharf MB Bixler EO Schweitzer PK Jacoby JA Soldatos CR August 1981 Dose response studies of quazepam Clin Pharmacol Ther 30 2 194 200 doi 10 1038 clpt 1981 148 PMID 6113910 S2CID 28714470 Nishiyama T Yamashita K Yokoyama T Imoto A Manabe M 2007 Effects of quazepam as a preoperative night hypnotic comparison with brotizolam J Anesth 21 1 7 12 doi 10 1007 s00540 006 0445 2 PMID 17285406 S2CID 24584685 Barnett A Iorio LC Ongini E 1982 The sedative hypnotic properties of quazepam a new hypnotic agent Arzneimittelforschung 32 11 1452 6 PMID 6129856 Lader M 1992 Rebound insomnia and newer hypnotics Psychopharmacology 108 3 248 55 doi 10 1007 BF02245108 PMID 1523276 S2CID 9051251 Murray A Bellville JW Comer W Danielson L April 1987 Respiratory effects of quazepam and pentobarbital J Clin Pharmacol 27 4 310 3 doi 10 1002 j 1552 4604 1987 tb03020 x PMID 2890670 S2CID 19696599 Billard W Crosby G Iorio L Chipkin R Barnett A 1988 Selective affinity of the benzodiazepines quazepam and 2 oxo quazepam for BZ1 binding site and demonstration of 3H 2 oxo quazepam as a BZ1 selective radioligand Life Sci 42 2 179 87 doi 10 1016 0024 3205 88 90681 9 PMID 2892106 Wamsley JK Hunt MA September 1991 Relative affinity of quazepam for type 1 benzodiazepine receptors in brain J Clin Psychiatry 52 Suppl 15 20 PMID 1680119 Martinez HT Serna CT 1982 Short term treatment with quazepam of insomnia in geriatric patients Clin Ther 5 2 174 8 PMID 6130842 Mendels J Stern S 1983 Evaluation of the short term treatment of insomnia in out patients with 15 milligrams of quazepam J Int Med Res 11 3 155 61 doi 10 1177 030006058301100305 PMID 6347747 S2CID 21652012 Aden GC Thatcher C December 1983 Quazepam in the short term treatment of insomnia in outpatients J Clin Psychiatry 44 12 454 6 PMID 6361006 Schaffler K Kauert G Wauschkuhn CH Klausnitzer W February 1989 Longitudinal study on pharmacodynamics and pharmacokinetics of acute steady state and withdrawn quazepam Arzneimittelforschung 39 2 276 83 PMID 2567171 FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class U S Food and Drug Administration FDA 23 September 2020 Retrieved 23 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H et al October 2003 Effects of foods on the pharmacokinetics and clinical efficacy of quazepam Nihon Shinkei Seishin Yakurigaku Zasshi 23 5 205 10 PMID 14653226 Rowlett JK Spealman RD Lelas S Cook JM Yin W January 2003 Discriminative stimulus effects of zolpidem in squirrel monkeys role of GABA A alpha1 receptors Psychopharmacology 165 3 209 15 doi 10 1007 s00213 002 1275 z PMID 12420154 S2CID 37632215 Iorio LC Barnett A Billard W July 1984 Selective affinity of 1 N trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites Life Sci 35 1 105 13 doi 10 1016 0024 3205 84 90157 7 PMID 6738302 Yezuita JP McCabe RT Barnett A Iorio LC Wamsley JK May 1988 Use of the selective benzodiazepine 1 BZ 1 ligand 3H 2 oxo quazepam SCH 15 725 to localize BZ 1 receptors in the rat brain Neurosci Lett 88 1 86 92 doi 10 1016 0304 3940 88 90320 5 PMID 2899863 S2CID 7031831 Tanaka M Suemaru K Watanabe S Cui R Li B Araki H July 2008 Comparison of short and long acting benzodiazepine receptor agonists with different receptor selectivity on motor coordination and muscle relaxation following thiopental induced anesthesia in mice J Pharmacol Sci 107 3 277 84 doi 10 1254 jphs FP0071991 PMID 18603831 Giorgi O Corda MG Gritti I Mariotti M Ongini E Biggio G July 1989 Binding sites for 3H 2 oxo quazepam in the brain of the cat evidence for heterogeneity of benzodiazepine recognition sites Neuropharmacology 28 7 715 8 doi 10 1016 0028 3908 89 90156 1 PMID 2569691 S2CID 39289029 Jochemsen R Breimer DD 1984 Pharmacokinetics of benzodiazepines metabolic pathways and plasma level profiles Curr Med Res Opin 8 Suppl 4 60 79 doi 10 1185 03007998409109545 PMID 6144464 Kales A 1990 Quazepam hypnotic efficacy and side effects Pharmacotherapy 10 1 1 10 discussion 10 2 doi 10 1002 j 1875 9114 1990 tb02545 x PMID 1969151 S2CID 33505418 Kales A Bixler EO Soldatos CR Vela Bueno A Jacoby J Kales JD December 1982 Quazepam and flurazepam long term use and extended withdrawal Clin Pharmacol Ther 32 6 781 8 doi 10 1038 clpt 1982 236 PMID 7140142 S2CID 24305854 Hilbert JM Chung M Maier G Gural R Symchowicz S Zampaglione N July 1984 Effect of sleep on quazepam kinetics Clin Pharmacol Ther 36 1 99 104 doi 10 1038 clpt 1984 146 PMID 6734056 S2CID 3039288 Wang JS DeVane CL 2003 Pharmacokinetics and drug interactions of the sedative hypnotics PDF Psychopharmacol Bull 37 1 10 29 doi 10 1007 BF01990373 PMID 14561946 S2CID 1543185 Archived from the original PDF on 2007 07 09 Zampaglione N Hilbert JM Ning J Chung M Gural R Symchowicz S 1985 Disposition and metabolic fate of 14C quazepam in man Drug Metab Dispos 13 1 25 9 PMID 2858372 Corda MG Sanna E Concas A et al August 1986 Enhancement of gamma aminobutyric acid binding by quazepam a benzodiazepine derivative with preferential affinity for type I benzodiazepine receptors J Neurochem 47 2 370 4 doi 10 1111 j 1471 4159 1986 tb04511 x PMID 3016172 S2CID 42138610 Hilbert JM Iorio L Moritzen V Barnett A Symchowicz S Zampaglione N July 1986 Relationships of brain and plasma levels of quazepam flurazepam and their metabolites with pharmacological activity in mice Life Sci 39 2 161 8 doi 10 1016 0024 3205 86 90451 0 PMID 3724367 Corda MG Giorgi O Longoni B Ongini E Montaldo S Biggio G 1988 Preferential affinity of 3H 2 oxo quazepam for type I benzodiazepine recognition sites in the human brain Life Sci 42 2 189 97 doi 10 1016 0024 3205 88 90682 0 PMID 2892107 Miller LG Galpern WR Byrnes JJ Greenblatt DJ October 1992 Benzodiazepine receptor binding of benzodiazepine hypnotics receptor and ligand specificity Pharmacol Biochem Behav 43 2 413 6 doi 10 1016 0091 3057 92 90170 K PMID 1359574 S2CID 24382596 Meldrum BS Chapman AG 1986 Benzodiazepine receptors and their relationship to the treatment of epilepsy Epilepsia 27 Suppl 1 S3 13 doi 10 1111 j 1528 1157 1986 tb05731 x PMID 3017690 S2CID 43227670 Corda MG Giorgi O Longoni BM et al 1988 Characterization of 3H 2 oxo quazepam binding in the human brain Prog Neuropsychopharmacol Biol Psychiatry 12 5 701 12 doi 10 1016 0278 5846 88 90015 2 PMID 2906158 S2CID 38611631 Roth TG Roehrs TA Koshorek GL Greenblatt DJ Rosenthal LD October 1997 Hypnotic effects of low doses of quazepam in older insomniacs J Clin Psychopharmacol 17 5 401 6 doi 10 1097 00004714 199710000 00009 PMID 9315991 Chapman AG De Sarro GB Premachandra M Meldrum BS September 1987 Bidirectional effects of beta carbolines in reflex epilepsy Brain Res Bull 19 3 337 46 doi 10 1016 0361 9230 87 90102 X PMID 3119161 S2CID 54366439 Mauri MC Gianetti S Pugnetti L Altamura AC 1993 Quazepam versus triazolam in patients with sleep disorders a double blind study Int J Clin Pharmacol Res 13 3 173 7 PMID 7901174 Wettstein JG October 1988 Effects of the novel benzodiazepine agonist quazepam on suppressed behavior of monkeys Eur J Pharmacol 155 1 2 19 25 doi 10 1016 0014 2999 88 90398 6 PMID 2907488 Mariotti M Ongini E August 1983 Differential effects of benzodiazepines on EEG activity and hypnogenic mechanisms of the brain stem in cats Arch Int Pharmacodyn Ther 264 2 203 19 PMID 6139096 Kawasaki H Urabe M Nuki C Yamamoto R Takasaki K Ohno H October 1987 Electroencephalographic study of Sch 161 quazepam a new benzodiazepine hypnotic in rats and rabbits Nippon Yakurigaku Zasshi in Japanese 90 4 221 38 doi 10 1254 fpj 90 221 PMID 3428780 Sieghart W July 1983 Several new benzodiazepines selectively interact with a benzodiazepine receptor subtype Neurosci Lett 38 1 73 8 doi 10 1016 0304 3940 83 90113 1 PMID 6136944 S2CID 42856742 Wamsley JK Golden JS Yamamura HI Barnett A 1985 Quazepam a sedative hypnotic selective for the benzodiazepine type 1 receptor autoradiographic localization in rat and human brain Clin Neuropharmacol 8 Suppl 1 S26 40 doi 10 1097 00002826 198508001 00005 PMID 2874881 S2CID 10557339 Griffiths RR Johnson MW 2005 Relative abuse liability of hypnotic drugs a conceptual framework and algorithm for differentiating among compounds J Clin Psychiatry 66 Suppl 9 31 41 PMID 16336040 External links Edit Quazepam Drug Information Portal U S National Library of Medicine Portal Medicine Retrieved from https en wikipedia org w index php title Quazepam amp oldid 1136000622, wikipedia, wiki, book, books, library,

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