Medicinal Chemistry Exam # 2
Terms
undefined, object
copy deck
-
Methacholine Chloride (Provocholine) -
* Acetyl ester of beta-methylcholine
* Used clinically as a diagnostic agent for bronchospasms (asthma)
* Is sufficiently stable in the body (unlike ACh)
* Although racemic mixture is used, activity resides in the (S)-enantiomer - Carbachol Chloride (Miostat)
-
* Carbamyl ester of choline (carbamate)
* Possesses both muscarinic & nicotinic activity (local effect)
* Rate of hydrolysis is slower & duration of action is longer
* used topically for glaucoma & eye surgery - Bethanechol Chloride (Urecholine)
-
* beta-methyl group & carbamate
* mostly muscarinic activity due to beta-methyl group
* very slow rate of hydrolysis, DOA: 1-6 hrs
* MOA: Stimulates cholinergic receptors in the smooth muscle of the urinary bladder & GIT
* Used primarily to treat or prevent post-surgical urinary retention & atony of muscles in GIT -
Pilocarpine HCl (Pilocar) -
* HCl salt of alkaloid from Pilocarpus jaborandi or P.microphyllus
* MOA: Directly stimulates cholinergic receptors in the eye causing:
- miosis (constriction of pupil)
- spasm of accommodation
- lowering of intraocular pressure
* used primarily as 0.5% solution in treatment of glaucoma
* systemic effects: copius sweating, salivation, & gastric secretion - Physostigmine (Eserine)
-
* alkaloid isolated from Physostigma venenosum
* MOA: inhibits AChE (Ki 10e-8 M)
* Monosubstituted carbamate
* Uses:
- treatment of glaucoma
- in ER, physostigmine salicylate has been used to treat overdoses of anticholinergics (e.g. atropine, tricyclic antidepressants)
- investigational in Alzheimer's disease - Neostigmine bromide (Prostigmin)
-
* dimethylcarbamate group meta to trimethylammonium group
* dimethylcarbamate enzyme is more resistant to hydrolysis
- longer DOA than physostigmine
* MOA: inhibit AChE (Ki 10e-7 M)
* inhibition of AChE by neostigmine unaffected by pH
* Uses:
- primarily to prevent post-surgical atony of muscles
- myasthenia gravis (skeletal muscle)
- ptosis: dropping of eyelid
- diplopia: double vision
- weakness of jaw muscles & proximal muscles - Pyridostigmine bromide (Mestinon)
-
* disubstituted carbamate
* fairly long DOA (3-6 hrs)
* used primarily in treatment of myasthenia gravis
* 1/5th as toxic as neostigmine - Edrophonium chloride (Tensilon)
-
* short DOA (minutes)
* used primarily as diagnostic agent for MG
* in ER, reversal of curare overdose
- used as IM, IV administration
* pharmacological challenge with Tensilon transitory but dramatic improvement in muscle function - Ambenonium chloride (Mytelase)
-
* used in treatment of MG for patients that do not respond to neostigmine or pyridostigmine
* derivative of oxalic acid
* long DOA - Demecarium bromide (Humorsol)
-
* very lipophilic
* used in treatment of wide angle glaucoma
* very long acting (~2 days)
* is a potent -> produce lot of cholinergic effect - Tacrine HCl (Cognex)
-
* tetrahydroacridine ring
* MOA: centrally-acting AChE inhibitor
* Uses: first drug approved for treatment of AD
* limited use (hepatotoxic)
* not selective for AChE or BuChE - Donepezil HCl (Aricept)
-
* used in treatment of AD & dementia
* MOA: centrally acting, reversible inhibitor of AChE
- selectivity for AChE (500-1200X) more than for BuChE
- greater affinity for AChE in brain than in periphery
- longer DOA
- no potential hepatotoxicity - Rivastimine (Exelon)
-
* aryl carbamate -> long DOA
* centrally acting AChE inhibitor (10 hr)
- psuedo - irreversible inhibitor
* used in treatment of AD