Benzatropine was approved for medical use in the United States in 1954.[4] It is available as a
generic medication.[4] In 2020, it was the 229th most commonly prescribed medication in the United States, with more than 2million prescriptions.[8][9] It is sold under the brand name Cogentin among others.[4]
Medical uses
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.[10] 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.
While some studies suggest that use of anticholinergics increases the risk of
tardive dyskinesia (a long-term side effect of antipsychotics),[11][12] other studies have found no association between anticholinergic exposure and risk of developing tardive dyskinesia,[13] although symptoms may be worsened.[14]
Drugs that decrease cholinergic transmission may impair storage of new information into long-term memory. Anticholinergic agents can also impair time perception.[15]
Pharmacology
Benzatropine is a centrally acting
anticholinergic/
antihistamine agent. It is a selective M1 muscarinic acetylcholine receptor antagonist. Benzatropine 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.[16]
Benzatropine has been also identified, by a high throughput screening approach, as a potent differentiating agent for
oligodendrocytes, possibly working through
M1 and
M3muscarinic receptors. In preclinical models for multiple sclerosis, benzatropine decreased clinical symptoms and enhanced re-myelination.[20]
Other animals
In veterinary medicine, benzatropine is used to treat
priapism in stallions.[21]
Naming
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,[2][3] and has been the official nonproprietary name in Australia since 2015.[22] 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).[3]
"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)[23] and was used in Australia until 2015, when it was harmonized with the INN.[22]
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.[24] The modified JAN is a hybrid form, benztropine mesilate.[23]
The misspelling benzotropine is also occasionally seen in the literature.
^DiMascio A, Bernardo DL, Greenblatt DJ, Marder JE (May 1976). "A controlled trial of amantadine in drug-induced extrapyramidal disorders". Archives of General Psychiatry. 33 (5): 599–602.
doi:
10.1001/archpsyc.1976.01770050055008.
PMID5066.
^Wszola BA, Newell KM, Sprague RL (August 2001). "Risk factors for tardive dyskinesia in a large population of youths and adults". Experimental and Clinical Psychopharmacology. 9 (3): 285–296.
doi:
10.1037/1064-1297.9.3.285.
PMID11534539.
^van Harten PN, Hoek HW, Matroos GE, Koeter M, Kahn RS (April 1998). "Intermittent neuroleptic treatment and risk for tardive dyskinesia: Curaçao Extrapyramidal Syndromes Study III". The American Journal of Psychiatry. 155 (4): 565–567.
doi:
10.1176/ajp.155.4.565.
PMID9546009.
^Yassa R (September 1988). "Tardive dyskinesia and anticholinergic drugs. A critical review of the literature". L'Encéphale. 14 Spec No (Spec No): 233–239.
PMID3063514.
^Gelenberg AJ, Van Putten T, Lavori PW, Wojcik JD, Falk WE, Marder S, et al. (June 1989). "Anticholinergic effects on memory: benztropine versus amantadine". Journal of Clinical Psychopharmacology. 9 (3): 180–185.
doi:
10.1097/00004714-198906000-00004.
PMID2661606.
S2CID27308127.
^Adler LA, Peselow E, Rosenthal M, Angrist B (1993). "A controlled comparison of the effects of propranolol, benztropine, and placebo on akathisia: an interim analysis". Psychopharmacology Bulletin. 29 (2): 283–286.
PMID8290678.
^Wilson DV, Nickels FA, Williams MA (November 1991). "Pharmacologic treatment of priapism in two horses". Journal of the American Veterinary Medical Association. 199 (9): 1183–1184.
doi:
10.2460/javma.1991.199.09.1183.
PMID1752772.