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Dexmethylphenidate

January 01, 1970

Dexmethylphenidate, sold under the brand name Focalin among others, is a potent central nervous system (CNS) stimulant used to treat attention deficit hyperactivity disorder (ADHD) in those over the age of five years.[3] It is taken by mouth.[3] The immediate release formulation lasts up to five hours while the extended release formulation lasts up to twelve hours.[4] It is the more active enantiomer of methylphenidate.[3]

Dexmethylphenidate
Clinical data
Trade namesFocalin, Focalin XR, others
Other namesd-threo-methylphenidate (D-TMP)
AHFS/Drugs.comMonograph
MedlinePlusa603014
License data
Dependence
liability		Physical: None[medical citation needed]; Psychological: High
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability11–52%
Protein binding30%
MetabolismLiver
Elimination half-life4 hours
ExcretionKidney
Identifiers
  • (R,R)-(+)-Methyl 2-phenyl-2-(2-piperidyl)acetate
CAS Number
  • 40431-64-9 N
  • hydrochloride: 19262-68-1
PubChem CID
  • 154101
  • hydrochloride: 154100
IUPHAR/BPS
  • 7554
DrugBank
  • DB06701 Y
  • hydrochloride: DBSALT001458
ChemSpider
  • 135807 Y
  • hydrochloride: 135806
UNII
  • M32RH9MFGP
  • hydrochloride: 1678OK0E08
KEGG
  • D07806 Y
  • hydrochloride: D03721 Y
ChEBI
  • CHEBI:51860 Y
ChEMBL
  • ChEMBL827 Y
  • hydrochloride: ChEMBL904
CompTox Dashboard (EPA)
  • DTXSID70893769
Chemical and physical data
FormulaC14H19NO2
Molar mass233.311 g·mol−1
3D model (JSmol)
  • Interactive image
  • hydrochloride: Interactive image
  • O=C([C@@H]([C@@H]1NCCCC1)C2=CC=CC=C2)OC

  • hydrochloride: Cl.[H][C@@](C(=O)OC)(C1=CC=CC=C1)[C@@]1([H])CCCCN1
  • InChI=1S/C14H19NO2/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3/t12-,13-/m1/s1 Y
  • Key:DUGOZIWVEXMGBE-CHWSQXEVSA-N Y

  • hydrochloride: InChI=1S/C14H19NO2.ClH/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12;/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3;1H/t12-,13-;/m1./s1
  • Key:JUMYIBMBTDDLNG-OJERSXHUSA-N
 NY (what is this?)  (verify)

Common side effects include abdominal pain, loss of appetite, and fever.[3] Serious side effects may include abuse, psychosis, sudden cardiac death, mania, anaphylaxis, seizures, and dangerously prolonged erection.[3] Safety during pregnancy and breastfeeding is unclear.[5] Dexmethylphenidate is a central nervous system (CNS) stimulant.[6][3] How it works in ADHD is unclear.[3]

Dexmethylphenidate was approved for medical use in the United States in 2001.[1] It is available as a generic medication.[3] In 2021, it was the 121st most commonly prescribed medication in the United States, with more than 4 million prescriptions.[7][8]

Medical uses edit

Dexmethylphenidate is used as a treatment for ADHD, usually along with psychological, educational, behavioral or other forms of treatment. It is proposed that stimulants help ameliorate the symptoms of ADHD by making it easier for the user to concentrate, avoid distraction, and control behavior. Placebo-controlled trials have shown that once-daily dexmethylphenidate XR was effective and generally well tolerated.[6]

Improvements in ADHD symptoms in children were significantly greater for dexmethylphenidate XR versus placebo.[6] It also showed greater efficacy than osmotic controlled-release oral delivery system (OROS) methylphenidate over the first half of the laboratory classroom day but assessments late in the day favoured OROS methylphenidate.[6]

Contraindications edit

This section is transcluded from Methylphenidate. (edit | history)

Methylphenidate is contraindicated for individuals with agitation, tics, glaucoma, heart defects or a hypersensitivity to any ingredients contained in methylphenidate pharmaceuticals.[9]

Pregnant women are advised to only use the medication if the benefits outweigh the potential risks.[10] Not enough human studies have been conducted to conclusively demonstrate an effect of methylphenidate on fetal development.[11] In 2018, a review concluded that it has not been teratogenic in rats and rabbits, and that it "is not a major human teratogen".[12]

Adverse effects edit

Part of this section is transcluded from Methylphenidate. (edit | history)

Products containing dexmethylphenidate have a side effect profile comparable to those containing methylphenidate.[13]

 
Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. Methylphenidate was ranked 13th in dependence, 12th in physical harm, and 18th in social harm.[14]

The most common side effects associated with methylphenidate (in standard and extended-release formulations) are appetite loss, dry mouth, anxiety/nervousness, nausea, and insomnia.[15] Gastrointestinal adverse effects may include abdominal pain and weight loss. Nervous system adverse effects may include akathisia (agitation/restlessness), irritability, dyskinesia (tics), lethargy (drowsiness/fatigue), and dizziness. Cardiac adverse effects may include palpitations, changes in blood pressure, and heart rate (typically mild), and tachycardia (rapid heart rate).[16] Ophthalmologic adverse effects may include blurred vision caused by pupil dilatation and dry eyes, with less frequent reports of diplopia and mydriasis.[contradictory][17][18]

Smokers with ADHD who take methylphenidate may increase their nicotine dependence, and smoke more often than before they began using methylphenidate, with increased nicotine cravings and an average increase of 1.3 cigarettes per day.[19]

There is some evidence of mild reductions in height with prolonged treatment in children.[20] This has been estimated at 1 centimetre (0.4 in) or less per year during the first three years with a total decrease of 3 centimetres (1.2 in) over 10 years.[21][22]

Hypersensitivity (including skin rash, urticaria, and fever) is sometimes reported when using transdermal methylphenidate. The Daytrana patch has a much higher rate of skin reactions than oral methylphenidate.[23]

Methylphenidate can worsen psychosis in people who are psychotic, and in very rare cases it has been associated with the emergence of new psychotic symptoms.[24] It should be used with extreme caution in people with bipolar disorder due to the potential induction of mania or hypomania.[25] There have been very rare reports of suicidal ideation, but some authors claim that evidence does not support a link.[20] Logorrhea is occasionally reported and visual hallucinations are very rarely reported.[17] Priapism is a very rare adverse event that can be potentially serious.[26]

U.S. Food and Drug Administration-commissioned studies in 2011 indicate that in children, young adults, and adults, there is no association between serious adverse cardiovascular events (sudden death, heart attack, and stroke) and the medical use of methylphenidate or other ADHD stimulants.[27]

Because some adverse effects may only emerge during chronic use of methylphenidate, a constant watch for adverse effects is recommended.[28]

A 2018 Cochrane review found that methylphenidate might be associated with serious side effects such as heart problems, psychosis, and death. The certainty of the evidence was stated as very low.[29]

The same review found tentative evidence that it may cause both serious and non-serious adverse effects in children.[29][a]

Overdose edit

The symptoms of a moderate acute overdose on methylphenidate primarily arise from central nervous system overstimulation; these symptoms include: vomiting, nausea, agitation, tremors, hyperreflexia, muscle twitching, euphoria, confusion, hallucinations, delirium, hyperthermia, sweating, flushing, headache, tachycardia, heart palpitations, cardiac arrhythmias, hypertension, mydriasis, and dryness of mucous membranes.[9][30] A severe overdose may involve symptoms such as hyperpyrexia, sympathomimetic toxidrome, convulsions, paranoia, stereotypy (a repetitive movement disorder), rhabdomyolysis, coma, and circulatory collapse.[9][30][31][b] A methylphenidate overdose is rarely fatal with appropriate care.[31] Following injection of methylphenidate tablets into an artery, severe toxic reactions involving abscess formation and necrosis have been reported.[32]

Treatment of a methylphenidate overdose typically involves the administration of benzodiazepines, with antipsychotics, α-adrenoceptor agonists and propofol serving as second-line therapies.[31]

 
Packaging of a formulation of methylphenidate advises against crushing the tablets. It is placed under Schedule X of the Indian drug scheduling system. Schedule X medications typically hold abusable medications such as barbiturates or stimulants such as amphetamines.

Addiction and dependence edit

Methylphenidate is a stimulant with an addiction liability and dependence liability similar to amphetamine. It has moderate liability among addictive drugs;[33][34] accordingly, addiction and psychological dependence are possible and likely when methylphenidate is used at high doses as a recreational drug.[34] When used above the medical dose range, stimulants are associated with the development of stimulant psychosis.[35]

Biomolecular mechanisms edit

Further information: Addiction § Biomolecular mechanisms

Methylphenidate has the potential to induce euphoria due to its pharmacodynamic effect (i.e., dopamine reuptake inhibition) in the brain's reward system. At therapeutic doses, ADHD stimulants do not sufficiently activate the reward system; consequently, when taken as directed in doses that are commonly prescribed for the treatment of ADHD, methylphenidate use lacks the capacity to cause an addiction.[34]

Interactions edit

This section is transcluded from Methylphenidate. (edit | history)

Methylphenidate may inhibit the metabolism of vitamin K anticoagulants, certain anticonvulsants, and some antidepressants (tricyclic antidepressants, and selective serotonin reuptake inhibitors). Concomitant administration may require dose adjustments, possibly assisted by monitoring of plasma drug concentrations.[36] There are several case reports of methylphenidate inducing serotonin syndrome with concomitant administration of antidepressants.[37][38][39][40]

When methylphenidate is coingested with ethanol, a metabolite called ethylphenidate is formed via hepatic transesterification,[41][42] not unlike the hepatic formation of cocaethylene from cocaine and ethanol. The reduced potency of ethylphenidate and its minor formation means it does not contribute to the pharmacological profile at therapeutic doses and even in overdose cases ethylphenidate concentrations remain negligible.[43][42]

Coingestion of alcohol (ethanol) also increases the blood plasma levels of d-methylphenidate by up to 40%.[44]

Liver toxicity from methylphenidate is extremely rare, but limited evidence suggests that intake of β-adrenergic agonists with methylphenidate may increase the risk of liver toxicity.[45]

Mode of activity edit

Methylphenidate is a catecholamine reuptake inhibitor that indirectly increases catecholaminergic neurotransmission by inhibiting the dopamine transporter (DAT) and norepinephrine transporter (NET),[46] which are responsible for clearing catecholamines from the synapse, particularly in the striatum and meso-limbic system.[47] Moreover, it is thought to "increase the release of these monoamines into the extraneuronal space."[2]

Although four stereoisomers of methylphenidate (MPH) are possible, only the threo diastereoisomers are used in modern practice. There is a high eudysmic ratio between the SS and RR enantiomers of MPH. Dexmethylphenidate (d-threo-methylphenidate) is a preparation of the RR enantiomer of methylphenidate.[48][49] In theory, D-TMP (d-threo-methylphenidate) can be anticipated to be twice the strength of the racemic product.[46][50]

Compd[51] DAT (Ki) DA (IC50) NET (Ki) NE (IC50)
D-TMP 161 23 206 39
L-TMP 2250 1600 >10K 980
DL-TMP 121 20 788 51

Pharmacology edit

Main article: Methylphenidate § Pharmacology

Dexmethylphenidate has a 4–6 hour duration of effect. A long-acting formulation, Focalin XR, which spans 12 hours is also available and has been shown to be as effective as DL (dextro-, levo-)-TMP (threo-methylphenidate) XR (extended release) (Concerta, Ritalin LA), with flexible dosing and good tolerability.[52][53] It has also been demonstrated to reduce ADHD symptoms in both children[54] and adults.[55] d-MPH has a similar side-effect profile to MPH[13] and can be administered without regard to food intake.[56]

Notes edit

  1. ^ "Our findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non-serious adverse events in children" "Concerning adverse events associated with the treatment, our systematic review of randomised clinical trials (RCTs) demonstrated no increase in serious adverse events, but a high proportion of participants suffered a range of non-serious adverse events."[29]
  2. ^ The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. ... However, fatalities are rare with appropriate care.[31]

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  53. ^ Silva R, Tilker HA, Cecil JT, Kowalik S, Khetani V, Faleck H, Patin J (2004). "Open-label study of dexmethylphenidate hydrochloride in children and adolescents with attention deficit hyperactivity disorder". Journal of Child and Adolescent Psychopharmacology. 14 (4): 555–63. doi:10.1089/cap.2004.14.555. PMID 15662147.
  54. ^ Arnold LE, Lindsay RL, Conners CK, Wigal SB, Levine AJ, Johnson DE, et al. (Winter 2004). "A double-blind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder". Journal of Child and Adolescent Psychopharmacology. 14 (4): 542–54. doi:10.1089/cap.2004.14.542. PMID 15662146.
  55. ^ Spencer TJ, Adler LA, McGough JJ, Muniz R, Jiang H, Pestreich L (June 2007). "Efficacy and safety of dexmethylphenidate extended-release capsules in adults with attention-deficit/hyperactivity disorder". Biological Psychiatry. 61 (12): 1380–7. doi:10.1016/j.biopsych.2006.07.032. PMID 17137560. S2CID 45976373.
  56. ^ Teo SK, Scheffler MR, Wu A, Stirling DI, Thomas SD, Stypinski D, Khetani VD (February 2004). "A single-dose, two-way crossover, bioequivalence study of dexmethylphenidate HCl with and without food in healthy subjects". Journal of Clinical Pharmacology. 44 (2): 173–8. doi:10.1177/0091270003261899. PMID 14747426. S2CID 20694072.

January 01, 1970
dexmethylphenidate, been, suggested, that, 1301, merged, into, this, article, discuss, proposed, since, november, 2023, sold, under, brand, name, focalin, among, others, potent, central, nervous, system, stimulant, used, treat, attention, deficit, hyperactivit. It has been suggested that CTx 1301 be merged into this article Discuss Proposed since November 2023 Dexmethylphenidate sold under the brand name Focalin among others is a potent central nervous system CNS stimulant used to treat attention deficit hyperactivity disorder ADHD in those over the age of five years 3 It is taken by mouth 3 The immediate release formulation lasts up to five hours while the extended release formulation lasts up to twelve hours 4 It is the more active enantiomer of methylphenidate 3 DexmethylphenidateClinical dataTrade namesFocalin Focalin XR othersOther namesd threo methylphenidate D TMP AHFS Drugs comMonographMedlinePlusa603014License dataUS DailyMed DexmethylphenidateDependenceliabilityPhysical None medical citation needed Psychological HighRoutes ofadministrationBy mouthATC codeN06BA11 WHO Legal statusLegal statusAU S8 Controlled drug CA Schedule III DE Anlage III Special prescription form required UK Class B US Schedule II 1 2 UN Psychotropic Schedule II In general Prescription only Pharmacokinetic dataBioavailability11 52 Protein binding30 MetabolismLiverElimination half life4 hoursExcretionKidneyIdentifiersIUPAC name R R Methyl 2 phenyl 2 2 piperidyl acetateCAS Number40431 64 9 Nhydrochloride 19262 68 1PubChem CID154101hydrochloride 154100IUPHAR BPS7554DrugBankDB06701 Yhydrochloride DBSALT001458ChemSpider135807 Yhydrochloride 135806UNIIM32RH9MFGPhydrochloride 1678OK0E08KEGGD07806 Yhydrochloride D03721 YChEBICHEBI 51860 YChEMBLChEMBL827 Yhydrochloride ChEMBL904CompTox Dashboard EPA DTXSID70893769Chemical and physical dataFormulaC 14H 19N O 2Molar mass233 311 g mol 13D model JSmol Interactive imagehydrochloride Interactive imageSMILES O C C H C H 1NCCCC1 C2 CC CC C2 OChydrochloride Cl H C C O OC C1 CC CC C1 C 1 H CCCCN1InChI InChI 1S C14H19NO2 c1 17 14 16 13 11 7 3 2 4 8 11 12 9 5 6 10 15 12 h2 4 7 8 12 13 15H 5 6 9 10H2 1H3 t12 13 m1 s1 YKey DUGOZIWVEXMGBE CHWSQXEVSA N Yhydrochloride InChI 1S C14H19NO2 ClH c1 17 14 16 13 11 7 3 2 4 8 11 12 9 5 6 10 15 12 h2 4 7 8 12 13 15H 5 6 9 10H2 1H3 1H t12 13 m1 s1Key JUMYIBMBTDDLNG OJERSXHUSA N N Y what is this verify Common side effects include abdominal pain loss of appetite and fever 3 Serious side effects may include abuse psychosis sudden cardiac death mania anaphylaxis seizures and dangerously prolonged erection 3 Safety during pregnancy and breastfeeding is unclear 5 Dexmethylphenidate is a central nervous system CNS stimulant 6 3 How it works in ADHD is unclear 3 Dexmethylphenidate was approved for medical use in the United States in 2001 1 It is available as a generic medication 3 In 2021 it was the 121st most commonly prescribed medication in the United States with more than 4 million prescriptions 7 8 Contents 1 Medical uses 2 Contraindications 3 Adverse effects 3 1 Overdose 3 2 Addiction and dependence 3 2 1 Biomolecular mechanisms 4 Interactions 5 Mode of activity 6 Pharmacology 7 Notes 8 ReferencesMedical uses editDexmethylphenidate is used as a treatment for ADHD usually along with psychological educational behavioral or other forms of treatment It is proposed that stimulants help ameliorate the symptoms of ADHD by making it easier for the user to concentrate avoid distraction and control behavior Placebo controlled trials have shown that once daily dexmethylphenidate XR was effective and generally well tolerated 6 Improvements in ADHD symptoms in children were significantly greater for dexmethylphenidate XR versus placebo 6 It also showed greater efficacy than osmotic controlled release oral delivery system OROS methylphenidate over the first half of the laboratory classroom day but assessments late in the day favoured OROS methylphenidate 6 Contraindications editThis section is transcluded from Methylphenidate edit history Methylphenidate is contraindicated for individuals with agitation tics glaucoma heart defects or a hypersensitivity to any ingredients contained in methylphenidate pharmaceuticals 9 Pregnant women are advised to only use the medication if the benefits outweigh the potential risks 10 Not enough human studies have been conducted to conclusively demonstrate an effect of methylphenidate on fetal development 11 In 2018 a review concluded that it has not been teratogenic in rats and rabbits and that it is not a major human teratogen 12 Adverse effects editPart of this section is transcluded from Methylphenidate edit history Products containing dexmethylphenidate have a side effect profile comparable to those containing methylphenidate 13 nbsp Addiction experts in psychiatry chemistry pharmacology forensic science epidemiology and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs Methylphenidate was ranked 13th in dependence 12th in physical harm and 18th in social harm 14 The most common side effects associated with methylphenidate in standard and extended release formulations are appetite loss dry mouth anxiety nervousness nausea and insomnia 15 Gastrointestinal adverse effects may include abdominal pain and weight loss Nervous system adverse effects may include akathisia agitation restlessness irritability dyskinesia tics lethargy drowsiness fatigue and dizziness Cardiac adverse effects may include palpitations changes in blood pressure and heart rate typically mild and tachycardia rapid heart rate 16 Ophthalmologic adverse effects may include blurred vision caused by pupil dilatation and dry eyes with less frequent reports of diplopia and mydriasis contradictory 17 18 Smokers with ADHD who take methylphenidate may increase their nicotine dependence and smoke more often than before they began using methylphenidate with increased nicotine cravings and an average increase of 1 3 cigarettes per day 19 There is some evidence of mild reductions in height with prolonged treatment in children 20 This has been estimated at 1 centimetre 0 4 in or less per year during the first three years with a total decrease of 3 centimetres 1 2 in over 10 years 21 22 Hypersensitivity including skin rash urticaria and fever is sometimes reported when using transdermal methylphenidate The Daytrana patch has a much higher rate of skin reactions than oral methylphenidate 23 Methylphenidate can worsen psychosis in people who are psychotic and in very rare cases it has been associated with the emergence of new psychotic symptoms 24 It should be used with extreme caution in people with bipolar disorder due to the potential induction of mania or hypomania 25 There have been very rare reports of suicidal ideation but some authors claim that evidence does not support a link 20 Logorrhea is occasionally reported and visual hallucinations are very rarely reported 17 Priapism is a very rare adverse event that can be potentially serious 26 U S Food and Drug Administration commissioned studies in 2011 indicate that in children young adults and adults there is no association between serious adverse cardiovascular events sudden death heart attack and stroke and the medical use of methylphenidate or other ADHD stimulants 27 Because some adverse effects may only emerge during chronic use of methylphenidate a constant watch for adverse effects is recommended 28 A 2018 Cochrane review found that methylphenidate might be associated with serious side effects such as heart problems psychosis and death The certainty of the evidence was stated as very low 29 The same review found tentative evidence that it may cause both serious and non serious adverse effects in children 29 a Overdose edit The symptoms of a moderate acute overdose on methylphenidate primarily arise from central nervous system overstimulation these symptoms include vomiting nausea agitation tremors hyperreflexia muscle twitching euphoria confusion hallucinations delirium hyperthermia sweating flushing headache tachycardia heart palpitations cardiac arrhythmias hypertension mydriasis and dryness of mucous membranes 9 30 A severe overdose may involve symptoms such as hyperpyrexia sympathomimetic toxidrome convulsions paranoia stereotypy a repetitive movement disorder rhabdomyolysis coma and circulatory collapse 9 30 31 b A methylphenidate overdose is rarely fatal with appropriate care 31 Following injection of methylphenidate tablets into an artery severe toxic reactions involving abscess formation and necrosis have been reported 32 Treatment of a methylphenidate overdose typically involves the administration of benzodiazepines with antipsychotics a adrenoceptor agonists and propofol serving as second line therapies 31 nbsp Packaging of a formulation of methylphenidate advises against crushing the tablets It is placed under Schedule X of the Indian drug scheduling system Schedule X medications typically hold abusable medications such as barbiturates or stimulants such as amphetamines Addiction and dependence edit Methylphenidate is a stimulant with an addiction liability and dependence liability similar to amphetamine It has moderate liability among addictive drugs 33 34 accordingly addiction and psychological dependence are possible and likely when methylphenidate is used at high doses as a recreational drug 34 When used above the medical dose range stimulants are associated with the development of stimulant psychosis 35 Biomolecular mechanisms edit Further information Addiction Biomolecular mechanisms Methylphenidate has the potential to induce euphoria due to its pharmacodynamic effect i e dopamine reuptake inhibition in the brain s reward system At therapeutic doses ADHD stimulants do not sufficiently activate the reward system consequently when taken as directed in doses that are commonly prescribed for the treatment of ADHD methylphenidate use lacks the capacity to cause an addiction 34 Interactions editThis section is transcluded from Methylphenidate edit history Methylphenidate may inhibit the metabolism of vitamin K anticoagulants certain anticonvulsants and some antidepressants tricyclic antidepressants and selective serotonin reuptake inhibitors Concomitant administration may require dose adjustments possibly assisted by monitoring of plasma drug concentrations 36 There are several case reports of methylphenidate inducing serotonin syndrome with concomitant administration of antidepressants 37 38 39 40 When methylphenidate is coingested with ethanol a metabolite called ethylphenidate is formed via hepatic transesterification 41 42 not unlike the hepatic formation of cocaethylene from cocaine and ethanol The reduced potency of ethylphenidate and its minor formation means it does not contribute to the pharmacological profile at therapeutic doses and even in overdose cases ethylphenidate concentrations remain negligible 43 42 Coingestion of alcohol ethanol also increases the blood plasma levels of d methylphenidate by up to 40 44 Liver toxicity from methylphenidate is extremely rare but limited evidence suggests that intake of b adrenergic agonists with methylphenidate may increase the risk of liver toxicity 45 Mode of activity editMethylphenidate is a catecholamine reuptake inhibitor that indirectly increases catecholaminergic neurotransmission by inhibiting the dopamine transporter DAT and norepinephrine transporter NET 46 which are responsible for clearing catecholamines from the synapse particularly in the striatum and meso limbic system 47 Moreover it is thought to increase the release of these monoamines into the extraneuronal space 2 Although four stereoisomers of methylphenidate MPH are possible only the threo diastereoisomers are used in modern practice There is a high eudysmic ratio between the SS and RR enantiomers of MPH Dexmethylphenidate d threo methylphenidate is a preparation of the RR enantiomer of methylphenidate 48 49 In theory D TMP d threo methylphenidate can be anticipated to be twice the strength of the racemic product 46 50 Compd 51 DAT Ki DA IC50 NET Ki NE IC50 D TMP 161 23 206 39 L TMP 2250 1600 gt 10K 980 DL TMP 121 20 788 51Pharmacology editMain article Methylphenidate Pharmacology Dexmethylphenidate has a 4 6 hour duration of effect A long acting formulation Focalin XR which spans 12 hours is also available and has been shown to be as effective as DL dextro levo TMP threo methylphenidate XR extended release Concerta Ritalin LA with flexible dosing and good tolerability 52 53 It has also been demonstrated to reduce ADHD symptoms in both children 54 and adults 55 d MPH has a similar side effect profile to MPH 13 and can be administered without regard to food intake 56 Notes edit Our findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non serious adverse events in children Concerning adverse events associated with the treatment our systematic review of randomised clinical trials RCTs demonstrated no increase in serious adverse events but a high proportion of participants suffered a range of non serious adverse events 29 The management of amphetamine dextroamphetamine and methylphenidate overdose is largely supportive with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines In cases where agitation delirium and movement disorders are unresponsive to benzodiazepines second line therapies include antipsychotics such as ziprasidone or haloperidol central alpha adrenoreceptor agonists such as dexmedetomidine or propofol However fatalities are rare with appropriate care 31 References edit a b Focalin dexmethylphenidate hydrochloride tablet DailyMed 24 June 2020 Retrieved 15 November 2020 a b Focalin XR dexmethylphenidate hydrochloride capsule extended release DailyMed 27 June 2020 Retrieved 15 November 2020 a b c d e f g h Dexmethylphenidate Hydrochloride Monograph for Professionals Drugs com American Society of Health System Pharmacists Retrieved 15 April 2019 Mosby s Drug Reference for Health Professions E Book Elsevier Health Sciences 2013 p 455 ISBN 9780323187602 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Ritalin enantiomers after oral administration Synapse 53 3 168 75 CiteSeerX 10 1 1 514 7833 doi 10 1002 syn 20046 PMID 15236349 S2CID 11664668 Davids E Zhang K Tarazi FI Baldessarini RJ February 2002 Stereoselective effects of methylphenidate on motor hyperactivity in juvenile rats induced by neonatal 6 hydroxydopamine lesioning Psychopharmacology 160 1 92 8 doi 10 1007 s00213 001 0962 5 PMID 11862378 S2CID 8037050 Williard RL Middaugh LD Zhu HJ Patrick KS February 2007 Methylphenidate and its ethanol transesterification metabolite ethylphenidate brain disposition monoamine transporters and motor activity Behavioural Pharmacology 18 1 39 51 doi 10 1097 FBP 0b013e3280143226 PMID 17218796 S2CID 20232871 McGough JJ Pataki CS Suddath R July 2005 Dexmethylphenidate extended release capsules for attention deficit hyperactivity disorder Expert Review of Neurotherapeutics 5 4 437 41 doi 10 1586 14737175 5 4 437 PMID 16026226 S2CID 6561452 Silva R Tilker HA Cecil JT Kowalik S Khetani V Faleck H Patin J 2004 Open label study of dexmethylphenidate hydrochloride in children and adolescents with attention deficit hyperactivity disorder Journal of Child and Adolescent Psychopharmacology 14 4 555 63 doi 10 1089 cap 2004 14 555 PMID 15662147 Arnold LE Lindsay RL Conners CK Wigal SB Levine AJ Johnson DE et al Winter 2004 A double blind placebo controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder Journal of Child and Adolescent Psychopharmacology 14 4 542 54 doi 10 1089 cap 2004 14 542 PMID 15662146 Spencer TJ Adler LA McGough JJ Muniz R Jiang H Pestreich L June 2007 Efficacy and safety of dexmethylphenidate extended release capsules in adults with attention deficit hyperactivity disorder Biological Psychiatry 61 12 1380 7 doi 10 1016 j biopsych 2006 07 032 PMID 17137560 S2CID 45976373 Teo SK Scheffler MR Wu A Stirling DI Thomas SD Stypinski D Khetani VD February 2004 A single dose two way crossover bioequivalence study of dexmethylphenidate HCl with and without food in healthy subjects Journal of Clinical Pharmacology 44 2 173 8 doi 10 1177 0091270003261899 PMID 14747426 S2CID 20694072 Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Dexmethylphenidate amp oldid 1204477256, wikipedia, wiki, book, books, library,

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