L-alphacetylmethadol (LAAM) effects on cardiac muscarinic receptors.
Chronic treatment with l-alphacetylmethadol (LAAM) reduced the number of myocardial muscarinic receptors measured by either antagonist binding with [3H]-quinuclidinyl benzilate ([3H]QNB) or agonist binding with [3H]-oxotremorine ([3H]OXO). The affinities of these binding sites for either [3H]QNB or [3H]OXO were unchanged by LAAM treatment. The ability of LAAM to antagonize the binding of [3H]QNB (125 pM) or [3H]OXO (8 nM) to myocardial membranes was tested. The measured affinity constant for LAAM was more than 200 times higher than atropine and 6 times lower than pilocarpine vs [3H]OXO binding, while the affinity constant for LAAM vs [3H]OXO was 1500 times higher than atropine, 30 times higher than methacholine but only 1.5 times higher than pilocarpine vs [3H]OXO binding. In isolated rat hearts, LAAM produced a concentration-dependent decrease in resting heart rate which was partially sensitive to inhibition by atropine. These data indicate that LAAM may act as a weak or partial agonist at myocardial muscarinic receptor sites.
Langley
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Department of Pharmacology and Toxicology, Wright State University, School of Medicine, Dayton, OH 45435.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D008691:Methadone / Q000031:analogs & derivatives*; D008692:Methadyl Acetate / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*
D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D010095:Oxotremorine; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D008692:Methadyl Acetate; D008691:Methadone