Pharmacological properties of acetorphan, a parenterally active "enkephalinase" inhibitor.

摘要: Acetorphan, i.e. N-[(R,S)-3-acetylmercapto-2-benzylpropanoyl]-glycine, benzyl ester, is a lipophilic derivative of Thiorphan, potent inhibitor "enkephalinase" (EC 3.4.24.11). On purified enkephalinase its inhibitory potency was approximately 1000 fold less than that Thiorphan but became close to the latter (nanomolar) when it incubated previously with cerebral membranes. After parenteral administration mice and rats (1-10 mg/kg) extensive inhibition shown by depressed enzyme activity in brain membranes from treated animals long-lasting potentiation analgesia elicited (D-Ala2,Met5)enkephalin (i.c.v.). This suggests acetorphan easily enters where active released. Parenteral series naloxone-reversible, opioid-like effects, most which were described intracerebral or other inhibitors. Antinociceptive effects found some tests (hot plate jump phenylbenzoquinone-induced writhing) not others licking tail withdrawal). "Antidepressant" effect "mouse despair" test antidiarrhoeal rat castor oil test. Acetorphan also significant increases decreases turnover indexes serotonin noradrenaline, respectively, mouse cortex. In chronically acetorphan, antinociceptive compound modified markedly no overt withdrawal symptom could be observed after either treatment interruption naloxone.