Variation in the affinity of amitriptyline for muscarine receptor subtypes.
The affinity of amitriptyline for muscarine M1 receptors was studied in the rat cerebral cortex and rabbit vas deferens utilizing binding studies as well as inhibition of carbachol-induced phosphoinositide hydrolysis in the cerebral cortex and blockade of the muscarinic prejunctional inhibition of sympathetic nerve stimulation in the rabbit vas deferens. The inhibition constants (KI) or dissociation constants (KB) obtained were approximately 6- to 20-fold lower than those obtained at muscarine M2 receptors in rat atria (binding and negative inotropic response) indicating that amitriptyline exhibits a degree of muscarine M1 receptor selectivity.
School of Pharmacology, Victorian College of Pharmacy (Monash University), Parkville, Australia.
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Choi
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Mitchelson
D000639:Amitriptyline / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000378:metabolism; D006868:Hydrolysis; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D010890:Pirenzepine / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000145:classification / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D000639:Amitriptyline; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D002217:Carbachol