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.

Citation

J Sharkey, M C Ritz, J A Schenden, R C Hanson, M J Kuhar. Cocaine inhibits muscarinic cholinergic receptors in heart and brain. The Journal of pharmacology and experimental therapeutics. 1988 Sep;246(3):1048-52

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PMID: 3047364

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