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.