Chapter 5: Cholinergic Drugs Prof,R.D.Ye 2012-09-29
Chapter 5: Cholinergic Drugs Prof. R.D. Ye 2012-09-29
Classes of cholinergic agonists Direct-acting Indirect-acting Receptor agonists Cholinesterase inhibitors Carbamates Choline esters PHYSOSTIGMINE Phosphates NEOSTIGMINE ISOFLUROPHATE ACETYLCHOLINE Alkaloids PYRIDOSTIGMINE Antidote BETHANECOL PILOCARPINE EDROPHONIUM PRALIDOXIMINE
Classes of cholinergic agonists Direct-acting Receptor agonists Choline esters ACETYLCHOLINE BETHANECOL Alkaloids PILOCARPINE Cholinesterase inhibitors Carbamates PHYSOSTIGMINE NEOSTIGMINE PYRIDOSTIGMINE EDROPHONIUM Phosphates ISOFLUROPHATE Antidote PRALIDOXIMINE Indirect-acting
Chemical structures of selected direct-acting cholinergic agonists 0 CH3 Quaternary ammonium HC-C-O-CH2-CH2-N*一 CHa CH3 Action chiefly muscarinic Acetylcholine HO 0 CH3 Hg H3C-C-O-CH-CH2-N*一 CH3 HgC CH2 -+N-( CH3 CH3 CHg CH3 Methacholine Muscarine (acetyl-B-methylcholine) 0 HaC-CH2 CH2 N-CH3 HN-0-0-cH-ch-N≤ CHa CHg CH3 Carbachol (carbamoylcholine) Pilocarpine 0 CHa CH3 Tertiary amine H2N-C-O-CH-CH2-N一 CH3 CHa Bethanechol (carbamoyl-B-methylcholine)
Chemical structures of selected direct-acting cholinergic agonists Tertiary amine Quaternary ammonium
Muscarinic agonists Receptor specificity Drugs mAChR nAchR Hydrolysis by AchE Acetylcholine +++ +++ +++ Carbachol ++ ++ (-) Methacholine +++ + Bethanechol +++ (-) (-) Muscarine +++ (-) (-) Pilocarpine + (-) (-) Muscarinic antagonists Atropine,scopolamine,and pirenzepine(relatively selective for M1 mAChR)
Muscarinic agonists Drugs Receptor specificity mAChR nAchR Hydrolysis by AchE Acetylcholine Carbachol Bethanechol Muscarine Pilocarpine Methacholine Muscarinic antagonists Atropine, scopolamine, and pirenzepine (relatively selective for M1 mAChR)
Choline esters: Absorption,metabolism,distribution Absorption:polarity-dependent (poorly distributed into CNS due to quaternary ammonium),intravenous, subcutaneous and intramuscular use for local effects Metabolism:Highly dependent on the susceptibility to acetylcholinesterase (AChE) Compound Susceptibility (AChE) Muscarinic Effect Acetylcholine chloride High (++++ High(limited by AChE) Methacholine chloride Low (+ Highest (++++ Carbachol chloride Negligible Medium (++ Bethanechol chloride Negligible Medium (++
Choline esters: Absorption, metabolism, distribution - Absorption: polarity-dependent (poorly distributed into CNS due to quaternary ammonium), intravenous, subcutaneous and intramuscular use for local effects - Metabolism: Highly dependent on the susceptibility to acetylcholinesterase (AChE) Compound Susceptibility (AChE) Muscarinic Effect Acetylcholine chloride High (++++) High (limited by AChE) Methacholine chloride Low (+) Highest (++++) Carbachol chloride Negligible Medium (++) Bethanechol chloride Negligible Medium (++)