INHIBITION OF MUSCARINIC RECEPTOR-STIMULATED PHOSPHOINOSITIDE METABOLISM BY COCAINE, NORCOCAINE AND COCAETHYLENE IN RAT-BRAIN

The interaction of cocaine, its metabolites norcocaine and benzoylecgo nine, and cocaethylene, which is formed following a combined cocaine a nd ethanol exposure, with muscarinic receptor binding and phosphoinosi tide metabolism was investigated in brain from immature rats. Cocaine and norcocaine inhibited binding of [H-3]telenzepine and carbachol-sti mulated phosphoinositide metabolism in cerebral cortex, while benzoyle cgonine was devoid of any inhibitory activity. Cocaethylene was the mo st potent inhibitor of both binding and phosphoinositide metabolism. T he effect of cocaine was more pronounced at the muscarinic receptors, but a small inhibition of histamine - and serotonin - stimulated phosp hoinositide metabolism was also observed.