132-17-2 Usage
Description
Benztropine mesylate, also known as Cogentin, is a synthetic compound with anticholinergic, antihistaminic, and local anesthetic properties. It is a centrally acting M1 muscarinic acetylcholine receptor antagonist and inhibits the dopamine transporter. Benztropine mesylate is a crystalline white powder, very soluble in water, and has a molecular weight of 403.54. It is supplied as a sterile injection for intravenous and intramuscular use under the brand name Cogentin by Merck.
Uses
Used in Neurology:
Benztropine mesylate is used as an antiparkinsonian agent for the treatment of Parkinson's disease. Its anticholinergic effect makes it applicable in this context, and it is about as potent an anticholinergic as atropine.
Used in Pharmacological Research:
Benztropine mesylate is used as an anti-histamine and dopamine re-uptake inhibitor. It has been utilized in research to study its target identification and mode of action against ebolavirus infection and to evaluate its effect on SLC6A19 (solute carrier family 6 member 19; B0AT1) in pharmacological animal studies.
Used in Clinical Trials:
Benztropine mesylate is currently in clinical trials for the treatment of chronic back pain. It shows anti-muscarinic effects comparable to Atropine and also demonstrates competitive anti-nicotinic action at the nAChR (nicotinic acetylcholine receptor).
Used in Multiple Sclerosis Treatment:
Benztropine mesylate enhances remyelination and significantly decreases clinical severity in the experimental autoimmune encephalomyelitis model of relapsing-remitting multiple sclerosis, either alone or in combination with immunosuppressive agents.
Used in Antiviral Research:
Benztropine mesylate has been found to inhibit hepatitis C virus infection, making it a potential candidate for antiviral research and treatment.
Originator
Cogentin,Merck Sharp and
Dohme,US,1954
Manufacturing Process
Diphenyldiazomethane was prepared by shaking 7.9 grams of benzophenone
hydrazone and 8.8 grams of yellow mercuric oxide in petroleum ether, filtering
and evaporating off the petroleum ether from the filtrate under reduced
pressure. To the residual diphenyldiazomethane 2.83 grams of tropine and 4.5
ml of benzene were added. The mixture was warmed in a pan of hot water at
about 85°C under reflux for 24 hours after which time the original purple color
had been largely discharged. The reaction mixture was dissolved by adding
benzene and water containing hydrochloric acid in excess of the quantity
theoretically required to form a salt. A rather large amount of water was
required since the tropine benzohydryl ether hydrochloride was not very
soluble and tended to separate as a third phase. The aqueous layer was
separated, washed with benzene and with ether and made alkaline with an
excess of sodium hydroxide. The resulting insoluble oil was extracted with
benzene.
The benzene extracts were dried over potassium carbonate and evaporated
under reduced pressure, leaving a residue of 4.1 grams. The residue (tropine
benzohydryl ether) was dissolved in ether and treated with hydrogen bromide
gas until an acidic reaction was obtained. The precipitate soon became
crystalline and was collected on a filter and dried. The tropine benzohydryl
ether hydrobromide weighed 4.1 grams. Recrystallization from absolute
ethanol gave 3.3 grams of first crop melting at 247°-248°C (dec.).
Twelve grains of tropine benzohydryl ether hydrobromide was converted to the
free base by warming with dilute aqueous sodium hydroxide. The oily base
was extracted with toluene. The toluene extract was washed with water and
then extracted with about 100 ml of water containing 28.1 ml of 1.10 N
methanesulfonic acid, (an equimolecular quantity). The toluene solution was
extracted twice more with fresh portions of water. The combined water
extracts were evaporated under reduced pressure. Residual water was
removed by dissolving the residue in absolute ethanol and evaporating under
reduced pressure several times. Residual alcohol was then removed by
dissolving the residue in acetone and evaporating under reduced pressure
several times. The resulting residue was recrystallized by dissolving in acetone
and adding ether. The crystalline precipitate was collected on a filter, washed with ether and dried at 56°C in vacuo. The tropine benzohydryl ether
methanesulfonate weighed 10.2 grams, MP 138°-140°C.
Therapeutic Function
Antiparkinsonian
Biological Activity
Benztropine mesylate is a centrally acting muscarinic acetylcholine receptor antagonist and dopamine transporter (DAT) inhibitor (IC50 = 118 nM). Benztropine mesylate has been used to treat the symptoms of Parkinson′s disease and is currently in clincial trials for chronic back pain.Benztropine mesylate serves as an inhibitor of breast cancer stem cells (BCSCs) in vitro and in vivo. It can help in improving the efficacy of chemotherapy in vitro. It is considered as an anti-cancer stem cell (CSC) drug, which can modify tumorigenic properties.
Clinical Use
The tremor and rigidity characteristic of parkinsonismare relieved by benztropine mesylate, and it is particularlyvaluable for those patients who cannot tolerate central excitation(e.g., aged patients). It may also have a useful effectin minimizing drooling, sialorrhea, masklike facies, oculogyriccrises, and muscular cramps.The usual caution exercised with any anticholinergic inglaucoma and prostatic hypertrophy is observed with thisdrug.
Safety Profile
Poison by ingestion,
intravenous, subcutaneous, and
intraperitoneal routes. Human systemic
effects by ingestion: psychotropic effects.
Mutation data reported. When heated to
decomposition it emits very toxic fumes of
NOx and SOx. See also ETHERS.
References
1) Zhang et al. (2001),?Synthesis and biological evaluation of tropane-like 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909) analogues; J. Med. Chem.,?44?3937
2) Schmitt?et al. (2008),?Interaction of cocaine-, benztropine-, and GBR12909-like compounds with wild-type and mutant human dopamine transporters: molecular features that differentially determine antagonist binding properties; J. Neurochem.,?107?928
3) Deshmukh?et al. (2013),?A regenerative approach to the treatment of multiple sclerosis; Nature,?502?327
4) Mingorance?et al. (2014),?Selective inhibition of hepatitis C virus infection by hydroxyzine and benztropine: Agents Chemother.,?58?3451
Check Digit Verification of cas no
The CAS Registry Mumber 132-17-2 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,3 and 2 respectively; the second part has 2 digits, 1 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 132-17:
(5*1)+(4*3)+(3*2)+(2*1)+(1*7)=32
32 % 10 = 2
So 132-17-2 is a valid CAS Registry Number.
InChI:InChI=1/C21H25NO.CH4O3S/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;1-5(2,3)4/h2-11,18-21H,12-15H2,1H3;1H3,(H,2,3,4)/t18-,19+,20+;
