benzatropine

Benzatropine is used to reduce extrapyramidal side effects of antipsychotic treatment. Benzatropine is also a second-line drug for the treatment of Parkinson's disease. It improves tremor, and may alleviate rigidity and bradykinesia.{{cite journal | vauthors = DiMascio A, Bernardo DL, Greenblatt DJ, Marder JE | title = A controlled trial of amantadine in drug-induced extrapyramidal disorders | journal = Archives of General Psychiatry | volume = 33 | issue = 5 | pages = 599–602 | date = May 1976 | pmid = 5066 | doi = 10.1001/archpsyc.1976.01770050055008 }} 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.

These are principally anticholinergic:

• Dry mouth
• Blurred vision
• Cognitive changes
• Drowsiness
• Constipation
• Urinary retention
• Tachycardia
• Anorexia
• Severe delirium and hallucinations (in overdose)

While some studies suggest that use of anticholinergics increases the risk of tardive dyskinesia (a long-term side effect of antipsychotics),{{cite journal | vauthors = Kane JM, Smith JM | title = Tardive dyskinesia: prevalence and risk factors, 1959 to 1979 | journal = Archives of General Psychiatry | volume = 39 | issue = 4 | pages = 473–481 | date = April 1982 | pmid = 6121548 | doi = 10.1001/archpsyc.1982.04290040069010 | s2cid = 10194153 }}{{cite journal | vauthors = Wszola BA, Newell KM, Sprague RL | title = Risk factors for tardive dyskinesia in a large population of youths and adults | journal = Experimental and Clinical Psychopharmacology | volume = 9 | issue = 3 | pages = 285–296 | date = August 2001 | pmid = 11534539 | doi = 10.1037/1064-1297.9.3.285 }} other studies have found no association between anticholinergic exposure and risk of developing tardive dyskinesia,{{cite journal | vauthors = van Harten PN, Hoek HW, Matroos GE, Koeter M, Kahn RS | title = Intermittent neuroleptic treatment and risk for tardive dyskinesia: Curaçao Extrapyramidal Syndromes Study III | journal = The American Journal of Psychiatry | volume = 155 | issue = 4 | pages = 565–567 | date = April 1998 | pmid = 9546009 | doi = 10.1176/ajp.155.4.565 }} although symptoms may be worsened.{{cite journal | vauthors = Yassa R | title = Tardive dyskinesia and anticholinergic drugs. A critical review of the literature | journal = L'Encéphale | volume = 14 Spec No | issue = Spec No | pages = 233–239 | date = September 1988 | pmid = 3063514 }}

Drugs that decrease cholinergic transmission may impair storage of new information into long-term memory. Anticholinergic agents can also impair time perception.{{cite journal | vauthors = Gelenberg AJ, Van Putten T, Lavori PW, Wojcik JD, Falk WE, Marder S, Galvin-Nadeau M, Spring B, Mohs RC, Brotman AW | title = Anticholinergic effects on memory: benztropine versus amantadine | journal = Journal of Clinical Psychopharmacology | volume = 9 | issue = 3 | pages = 180–185 | date = June 1989 | pmid = 2661606 | doi = 10.1097/00004714-198906000-00004 | s2cid = 27308127 }}

Benzatropine is a centrally acting anticholinergic and antihistamine. In terms of its anticholinergic activity, it is specifically an antimuscarinic and acts a selective muscarinic acetylcholine M₁ and M₃ receptor antagonist.{{cite journal | vauthors = Lakstygal AM, Kolesnikova TO, Khatsko SL, Zabegalov KN, Volgin AD, Demin KA, Shevyrin VA, Wappler-Guzzetta EA, Kalueff AV | title = DARK Classics in Chemical Neuroscience: Atropine, Scopolamine, and Other Anticholinergic Deliriant Hallucinogens | journal = ACS Chem Neurosci | volume = 10 | issue = 5 | pages = 2144–2159 | date = May 2019 | pmid = 30566832 | doi = 10.1021/acschemneuro.8b00615 | url = }} Benzatropine partially blocks cholinergic activity in the basal ganglia. 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.MIMS Australia Pty Ltd. MIMS.

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.{{cite journal | vauthors = 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 | title = A regenerative approach to the treatment of multiple sclerosis | journal = Nature | volume = 502 | issue = 7471 | pages = 327–332 | date = October 2013 | pmid = 24107995 | pmc = 4431622 | doi = 10.1038/nature12647 | bibcode = 2013Natur.502..327D }}

In addition to its anticholinergic activity, benztropine has been found to increase the availability of dopamine by blocking its reuptake and storage in central sites, and as a result, increasing dopaminergic activity. Benzatropine and analogues are atypical dopamine reuptake inhibitors,{{cite journal | vauthors = Hiranita T, Kohut SJ, Soto PL, Tanda G, Kopajtic TA, Katz JL | title = Preclinical efficacy of N-substituted benztropine analogs as antagonists of methamphetamine self-administration in rats | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 348 | issue = 1 | pages = 174–191 | date = January 2014 | pmid = 24194527 | pmc = 3868882 | doi = 10.1124/jpet.113.208264 }} which might make them useful for people with akathisia secondary to antipsychotic therapy.{{cite journal | vauthors = Adler LA, Peselow E, Rosenthal M, Angrist B | title = A controlled comparison of the effects of propranolol, benztropine, and placebo on akathisia: an interim analysis | journal = Psychopharmacology Bulletin | volume = 29 | issue = 2 | pages = 283–286 | year = 1993 | pmid = 8290678 }}

Benzatropine also acts as a functional inhibitor of acid sphingomyelinase (FIASMA).{{cite journal | vauthors = Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer TW, Spitzer GM, Liedl KR, Gulbins E, Tripal P | title = Identification of novel functional inhibitors of acid sphingomyelinase | journal = PLOS ONE | volume = 6 | issue = 8 | pages = e23852 | year = 2011 | pmid = 21909365 | pmc = 3166082 | doi = 10.1371/journal.pone.0023852 | doi-access = free | bibcode = 2011PLoSO...623852K }}

In veterinary medicine, benzatropine is used to treat priapism in stallions.{{cite journal | vauthors = Wilson DV, Nickels FA, Williams MA | title = Pharmacologic treatment of priapism in two horses | journal = Journal of the American Veterinary Medical Association | volume = 199 | issue = 9 | pages = 1183–1184 | date = November 1991 | doi = 10.2460/javma.1991.199.09.1183 | pmid = 1752772 }}

Since 1959, benzatropine is the official international nonproprietary name of the medication under the INN scheme, the medication naming system coordinated by the World Health Organization; it is also the British Approved Name (BAN) given in the British Pharmacopoeia, and has been the official nonproprietary name in Australia since 2015. Regional variations of the "a" spelling are also used in French, Italian, Portuguese, and Spanish, as well as Latin (all medications are assigned a Latin name by WHO).

"Benztropine" is the official United States Adopted Name (USAN), the medication naming system coordinated by the USAN Council, co-sponsored by the American Medical Association (AMA), the United States Pharmacopeial Convention (USP), and the American Pharmacists Association (APhA). It is also the Japanese Accepted Name (JAN){{KEGG compound|D00778}} and was used in Australia until 2015, when it was harmonized with the INN.{{cite web |url=https://www.tga.gov.au/updating-medicine-ingredient-names-list-affected-ingredients |title=Updating medicine ingredient names - list of affected ingredients |publisher=Therapeutic Goods Administration |date=23 November 2015 |access-date=1 December 2020 |archive-date=27 November 2020 |archive-url=https://web.archive.org/web/20201127054118/https://www.tga.gov.au/updating-medicine-ingredient-names-list-affected-ingredients |url-status=live }}

Both names may be modified to account for the methanesulfonate salt as which the medication is formulated: the modified INN (INNm) and BAN (BANM) is benzatropine mesilate, while the modified USAN is benztropine mesylate.{{Cite book|editor=Sweetman, Sean C. |chapter=Antiparkinsonian Drugs |title=Martindale: The Complete Drug Reference |edition=36th |year=2009 |pages=797|publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1}} The modified JAN is a hybrid form, benztropine mesilate.

The misspelling benzotropine is also occasionally seen in the literature.

{{Reflist}}

{{Antiparkinson}}

{{Histamine receptor modulators}}

{{Monoamine reuptake inhibitors}}

{{Muscarinic acetylcholine receptor modulators}}

{{Portal bar | Medicine}}

Category:Diphenylmethanol ethers

Category:Dopamine reuptake inhibitors

Category:H1 receptor antagonists

Category:M1 receptor antagonists

Category:M2 receptor antagonists

Category:M3 receptor antagonists

Category:M4 receptor antagonists

Category:M5 receptor antagonists

Category:Oneirogens

Category:Tardive dyskinesia

Category:Tropanes

Category:Wikipedia medicine articles ready to translate