Alteration of in vivo and in vitro effects of heroin by esterase inhibition.
Selective inhibition of peripheral esterases by tri-ortho-tolyl phosphate in the mouse resulted in an increase in the analgetic activity of heroin, without affecting the activity of morphine. In vitro inhibition of esterases by paraoxon reduced the affinity of heroin for the opiate receptor, while that of morphine was unaffected. These results suggest that both central and peripheral esterases are involved in the metabolism of heroin and that interference with critical esterases can alter its pharmacologic and toxicologic effects.
D000085:Acetates; D019342:Acetic Acid; D000698:Analgesia; D000818:Animals; D004347:Drug Interactions; D004950:Esterases / Q000037:antagonists & inhibitors*; D003932:Heroin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009022:Morphine Derivatives / Q000494:pharmacology; D010261:Paraoxon / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D014317:Tritolyl Phosphates / Q000494:pharmacology
D000085:Acetates; D009022:Morphine Derivatives; D011957:Receptors, Opioid; D014317:Tritolyl Phosphates; D003932:Heroin; D009020:Morphine; D004950:Esterases; C026979:6-O-monoacetylmorphine; D019342:Acetic Acid; D010261:Paraoxon; C025541:tri-o-cresyl phosphate