関: benztropine

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/08 06:33:35」(JST)

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Benzatropine (INN), also known as benztropine (USAN, BAN), is an anticholinergic marketed under the trade name Cogentin which is used in the treatment of Parkinson's disease, Parkinsonism, and dystonia.

Medical uses

Benzatropine is an anticholinergic drug used in patients to reduce the side effects of antipsychotic treatment. Benzatropine is also a second-line drug for the treatment of Parkinson's disease. It improves tremor, but not rigidity and bradykinesia. Benzatropine is also sometimes used for the treatment of dystonia, a rare disorder that causes abnormal muscle contraction, resulting in twisting postures of limbs, trunk, or face.

Adverse effects

These are principally anticholinergic:

Dry mouth
Blurred vision
Cognitive changes
Constipation
Urinary retention
Tachycardia
Anorexia
Psychosis (in overdose)

While some studies suggest that use of anticholinergics increases the risk of tardive dyskinesia (a long-term side effect of antipsychotics),^[1]^[2] other studies have found no association between anticholinergic exposure and risk of developing tardive dyskinesia,^[3] although symptoms may be worsened.^[4]

Drugs that decrease cholinergic transmission may impair storage of new information into long-term memory. Anticholinergic agents can also impair time perception.^[5]

Pharmacology

Benzatropine is a centrally acting anticholinergic/antihistamine agent. It is a selective M1 muscarinic acetylcholine receptor antagonist. Benztropine partially blocks cholinergic activity in the basal ganglia and has also been shown to increase the availability of dopamine by blocking its reuptake and storage in central sites, and as a result, increasing dopaminergic activity. Animal studies have indicated that anticholinergic activity of benzatropine is approximately one-half that of atropine, while its antihistamine activity approaches that of mepyramine. Its anticholinergic effects have been established as therapeutically significant in the management of Parkinsonism. Benzatropine antagonizes the effect of acetylcholine, decreasing the imbalance between the neurotransmitters acetylcholine and dopamine, which may improve the symptoms of early Parkinson's disease.^[6]

Benzatropine analogues are atypical dopamine reuptake inhibitors,^[7] which might make them useful for people with extrapyramidal symptoms who take antipsychotics.^{[citation needed]}

Benzatropine also acts as a functional inhibitor of acid sphingomyelinase (FIASMA).^[8]

Benzatropine has been also identified, by a high throughput screening approach, as a potent differentiating agent for oligodendrocytes, possibly working through M1 and M3 muscarinic receptors. In preclinical models for multiple sclerosis, benzatropine decreased clinical symptoms and enhanced re-myelination (Deshmukh et al., Nature 2013).^[9]

References

^ Kane JM, Smith JM (1982). "Tardive dyskinesia: Prevalence and risk factors, 1959 to 1979". Archives of General Psychiatry 39 (4): 473–81. doi:10.1001/archpsyc.1982.04290040069010. PMID 6121548.
^ Wszola BA, Newell KM, Sprague RL (2001). "Risk factors for tardive dyskinesia in a large population of youths and adults". Experimental and Clinical Psychopharmacology 9 (3): 285–96. doi:10.1037/1064-1297.9.3.285. PMID 11534539.
^ van Harten PN, Hoek HW, Matroos GE, Koeter M, Kahn RS (1998). "Intermittent neuroleptic treatment and risk for tardive dyskinesia: Curaçao Extrapyramidal Syndromes Study III". The American Journal of Psychiatry 155 (4): 565–7. PMID 9546009.
^ Yassa R (1988). "Tardive dyskinesia and anticholinergic drugs. A critical review of the literature". L'Encephale 14 (Spec No): 233–9. PMID 3063514.
^ Gelenberg AJ, Van Putten T, Lavori PW, Wojcik JD, Falk WE, Marder S, Galvin-Nadeau M, Spring B, Mohs RC, Brotman AW. (1989). "Anticholinergic effects on memory: benztropine versus amantadine.". Clinical Psychopharmacology 9 (3): 180–5. doi:10.1097/00004714-198906000-00004. PMID 2661606.
^ MIMS Australia Pty Ltd. MIMS.
^ Hiranita T, Kohut SJ, Soto PL, Tanda G, Kopajtic TA, Katz JL. (2014). "Preclinical efficacy of N-substituted benztropine analogs as antagonists of methamphetamine self-administration in rats". J Pharmacol Exp Ther. 348 (1): 174–91. doi:10.1124/jpet.113.208264. PMC 3868882. PMID 24194527.
^ Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P (2011). "Identification of novel functional inhibitors of acid sphingomyelinase". PLoS ONE 6 (8): e23852. doi:10.1371/journal.pone.0023852. PMC 3166082. PMID 21909365.
^ Deshmukh VA, Tardif V, Lyssiotis CA, Green CC, Kerman B, Kim HJ, Padmanabhan K, Swoboda JG, Ahmad I, Kondo T, Gage FH, Theofilopoulos AN, Lawson BR, Schultz PG, Lairson LL. (2013). "A regenerative approach to the treatment of multiple sclerosis". Nature 502 (7471): 327–332. doi:10.1038/nature12647. PMID 24107995.

English Journal

Drug-induced parkinsonism following chronic methamphetamine use by a patient on haloperidol decanoate.

Matthew BJ1, Gedzior JS2.
International journal of psychiatry in medicine.Int J Psychiatry Med.2015 Nov 2. pii: 0091217415612736. [Epub ahead of print]
This report attempts to highlight that use of an antipsychotic and concurrent chronic use of methamphetamine can cause drug-induced parkinsonism. Methamphetamine is usually not encountered in the list of agents that induce drug-induced parkinsonism and so its consideration particularly during chroni
PMID 26526398

Persistence of racial disparities in prescription of first-generation antipsychotics in the USA.

Cook TB1, Reeves GM2, Teufel J1, Postolache TT2,3,4.
Pharmacoepidemiology and drug safety.Pharmacoepidemiol Drug Saf.2015 Nov;24(11):1197-206. doi: 10.1002/pds.3819. Epub 2015 Jul 1.
PURPOSE: The aim of this study was to estimate the prevalence of first-generation antipsychotics (FGA) prescribed for treatment of psychiatric and neurological conditions and use of benztropine to reduce extrapyramidal side effects (EPS) by patient race/ethnicity in a nationally representative sampl
PMID 26132170

Low Dose Loxapine: Neuromotor Side Effects and Tolerability in Autism Spectrum Disorders.

Hellings JA1,2, Jadhav M2,3, Jain S1,4, Jadhav S2, Genovese A2.
Journal of child and adolescent psychopharmacology.J Child Adolesc Psychopharmacol.2015 Oct;25(8):618-24. doi: 10.1089/cap.2014.0145.
OBJECTIVE: New and repurposed drugs are urgently needed to treat individuals with autism spectrum disorders (ASD). Loxapine (LOX) in low doses of 5-15 mg/day resembles an atypical antipsychotic (Stahl 2002 ). Our recent open pilot study of LOX found significant behavioral improvements and overall
PMID 26485086

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リンク元	「ベンザトロピン」
拡張検索	「etybenzatropine」

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Benzatropine
Systematic (IUPAC) name
	(3-endo)-3-(Diphenylmethoxy)-8-methyl-8-azabicyclo[3.2.1]octane
Clinical data
Trade names	Cogentin
AHFS/Drugs.com	monograph
Pregnancy; category	US: C (Risk not ruled out);
Legal status	US: ℞-only;
Routes of; administration	Oral, IM, IV
Pharmacokinetic data
Metabolism	Hepatic
Half-life	12-24 hours
Excretion	Urine
Identifiers
CAS Registry Number	86-13-5
ATC code	N04AC01
PubChem	CID 1201549
DrugBank	DB00245
ChemSpider	16736541
UNII	1NHL2J4X8K
ChEBI	CHEBI:3048
ChEMBL	CHEMBL1201203
Synonyms	Benztropine
Chemical data
Formula	C21H25NO
Molecular mass	307.429 g/mol
	SMILES CN4[C@@H]1CC[C@H]4C[C@H](C1)OC(c2ccccc2)c3ccccc3;
	InChI InChI=1S/C21H25NO/c1-22-18-12-13-19(22)15-20(14-18)23-21(16-8-4-2-5-9-16)17-10-6-3-7-11-17/h2-11,18-21H,12-15H2,1H3/t18-,19+,20+ ; Key:GIJXKZJWITVLHI-PMOLBWCYSA-N ;
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英: benzatropine
関: ベンズトロピン

「etybenzatropine」

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[1] Kane JM, Smith JM (1982). "Tardive dyskinesia: Prevalence and risk factors, 1959 to 1979". Archives of General Psychiatry 39 (4): 473–81. doi:10.1001/archpsyc.1982.04290040069010. PMID 6121548.

[pmid11534539-2] Wszola BA, Newell KM, Sprague RL (2001). "Risk factors for tardive dyskinesia in a large population of youths and adults". Experimental and Clinical Psychopharmacology 9 (3): 285–96. doi:10.1037/1064-1297.9.3.285. PMID 11534539.

[pmid9546009-3] van Harten PN, Hoek HW, Matroos GE, Koeter M, Kahn RS (1998). "Intermittent neuroleptic treatment and risk for tardive dyskinesia: Curaçao Extrapyramidal Syndromes Study III". The American Journal of Psychiatry 155 (4): 565–7. PMID 9546009.

[4] Yassa R (1988). "Tardive dyskinesia and anticholinergic drugs. A critical review of the literature". L'Encephale 14 (Spec No): 233–9. PMID 3063514.

[pmid2661606-5] Gelenberg AJ, Van Putten T, Lavori PW, Wojcik JD, Falk WE, Marder S, Galvin-Nadeau M, Spring B, Mohs RC, Brotman AW. (1989). "Anticholinergic effects on memory: benztropine versus amantadine.". Clinical Psychopharmacology 9 (3): 180–5. doi:10.1097/00004714-198906000-00004. PMID 2661606.

[6] MIMS Australia Pty Ltd. MIMS.

[pmid24194527-7] Hiranita T, Kohut SJ, Soto PL, Tanda G, Kopajtic TA, Katz JL. (2014). "Preclinical efficacy of N-substituted benztropine analogs as antagonists of methamphetamine self-administration in rats". J Pharmacol Exp Ther. 348 (1): 174–91. doi:10.1124/jpet.113.208264. PMC 3868882. PMID 24194527.

[pmid18504571-8] Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P (2011). "Identification of novel functional inhibitors of acid sphingomyelinase". PLoS ONE 6 (8): e23852. doi:10.1371/journal.pone.0023852. PMC 3166082. PMID 21909365.

[pmid24107995-9] Deshmukh VA, Tardif V, Lyssiotis CA, Green CC, Kerman B, Kim HJ, Padmanabhan K, Swoboda JG, Ahmad I, Kondo T, Gage FH, Theofilopoulos AN, Lawson BR, Schultz PG, Lairson LL. (2013). "A regenerative approach to the treatment of multiple sclerosis". Nature 502 (7471): 327–332. doi:10.1038/nature12647. PMID 24107995.

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benzatropine