Benzatropine

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
Biological half-life	12-24 hours
Excretion	Urine
Identifiers
CAS Number	86-13-5 Y
ATC code	N04AC01 (WHO)
PubChem	CID: 1201549
IUPHAR/BPS	7601
DrugBank	DB00245 N
ChemSpider	16736541 Y
UNII	1NHL2J4X8K Y
ChEBI	CHEBI:3048 Y
ChEMBL	CHEMBL1201203 N
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+ Y Key:GIJXKZJWITVLHI-PMOLBWCYSA-N Y
NY (what is this?)  (verify)

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), other studies have found no association between anticholinergic exposure and risk of developing tardive dyskinesia, although symptoms may be worsened.

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

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.

Benzatropine analogues are atypical dopamine reuptake inhibitors, which might make them useful for people with extrapyramidal symptoms who take antipsychotics.

Benzatropine also acts as a functional inhibitor of acid sphingomyelinase (FIASMA).

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.

See also

• List of benzatropine analogues
• CRL-40,941