Cocaine inhibits muscarinic cholinergic receptors in heart and brain.
(-)-Cocaine inhibits M2 muscarinic cholinergic binding measured with [3H]quinuclidinyl benzilate in heart and brain with a Ki of 18.8 microM. The cyclic nucleotide 5'-guanylylimidodiphosphate does not shift the competition curve, suggesting that (-)-cocaine is an antagonist. (-)-Cocaine also reverses the methacholine-induced inhibition of guinea pig atrial contractions at a similar concentration. Although (+)-cocaine is about 8-fold more potent than (-)-cocaine, (+)-cocaine is not present in extracts of the coca plant. Of the many compounds tested, only (-)-cocaine and lidocaine have a higher affinity at M2 muscarinic receptors than at M1 receptors; other compounds such as (+)-cocaine, norcocaine, procaine and dimethocaine are equipotent at the M1 and M2 subtypes. These results indicate that cocaine can act as an antimuscarinic agent, particularly at higher, toxic doses.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010890:Pirenzepine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*
D008688:Methacholine Compounds; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D003042:Cocaine