Cocaine inhibits muscarinic cholinergic receptors in heart and brain.

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Sharkey J, Ritz MC, Schenden JA, Hanson RC, Kuhar MJ

Cocaine inhibits muscarinic cholinergic receptors in heart and brain.

J Pharmacol Exp Ther. 1988 Sep;246(3):1048-52.

PubMed ID

3047364 [ View in PubMed

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Abstract

(-)-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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cocaine	Muscarinic acetylcholine receptor M1	Protein	Humans	Unknown	Antagonist	Details
Cocaine	Muscarinic acetylcholine receptor M2	Protein	Humans	Unknown	Antagonist	Details
Cocaine	Sigma non-opioid intracellular receptor 1	Protein	Humans	Unknown	Agonist	Details