Inhibition of muscarinic receptor-stimulated phosphoinositide metabolism by cocaine, norcocaine and cocaethylene in rat brain.
The interaction of cocaine, its metabolites norcocaine and benzoylecgonine, and cocaethylene, which is formed following a combined cocaine and ethanol exposure, with muscarinic receptor binding and phosphoinositide metabolism was investigated in brain from immature rats. Cocaine and norcocaine inhibited binding of [3H]telenzepine and carbachol-stimulated phosphoinositide metabolism in cerebral cortex, while benzoylecgonine was devoid of any inhibitory activity. Cocaethylene was the most potent inhibitor of both binding and phosphoinositide metabolism. The effect of cocaine was more pronounced at the muscarinic receptors, but a small inhibition of histamine--and serotonin--stimulated phosphoinositide metabolism was also observed.
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Department of Environmental Health, University of Washington, Seattle 98195.
Costa
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D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002217:Carbachol / Q000037:antagonists & inhibitors; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D008297:Male; D018727:Muscarinic Antagonists; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D010276:Parasympatholytics / Q000493:pharmacokinetics; D010716:Phosphatidylinositols / Q000378:metabolism*; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D018727:Muscarinic Antagonists; D014179:Neurotransmitter Uptake Inhibitors; D010276:Parasympatholytics; D010716:Phosphatidylinositols; C046338:telenzepine; D010890:Pirenzepine; C008671:norcocaine; C005618:benzoylecgonine; D002217:Carbachol; C066444:cocaethylene; D003042:Cocaine