Add time:08/19/2019         Source:sciencedirect.com

The effect of phelorphan (mercaptoacetyl-Phe-Phe), an inhibitor of various enkephalin-degrading enzymes, was tested in the mouse hot plate test and its efficacy to prevent endogenous enkephalin degradation in mouse striatum was determined. The i.c.v. injection of phelorphan (50 μg) increased the [Met5]enkephalin immunoreactivity by 41% in the extrasynaptosomal fraction of mouse striatum compared to a 43% increase induced by i.c.v. administration of thiorphan (50 μg) + bestatin (75 μg). Jump latency in the mouse hot plate test was significantly prolonged by phelorphan (25 μg i.c.v.). The analgesic effect of phelorphan was the same as that of thiorphan (25 μg i.c.v.) + bestatin (25 μg i.c.v.) and was antagonized by pretreatment with naloxone. These results suggest that phelorphan induces naloxone-reversible analgesia by elevation of [Met5]enkephalin levels in the synaptic cleft.

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