Analgesic and convulsant effects of guanidinoethylmercaptosuccinic acid (GEMSA)--a potent enkephalin convertase inhibitor.
We studied behavioral effects of the intraventricularly and intrathecally administered guanidinoethylmercaptosuccinic acid (GEMSA) - a potent inhibitor of enkephalin convertase. When given intraventricularly in doses of 3 and 6 micrograms, GEMSA elicited analgesia; after doses of 12.5 and 25 micrograms the explosive motor behavior and convulsions occurred. Following the intrathecal administration of GEMSA (12.5, 25 and 50 micrograms), an increase in the tail-flick latency was observed; moreover that drug potentiated analgesic effects of the intrathecally applied Met5-enkephalin-Arg6-Phe7 and Met5-enkephalin-Arg6-Gly7-Leu8. All the above effects of GEMSA were significantly attenuated by naloxone. The rats subjected to chronic pain showed a weaker analgesic response to the intrathecally injected GEMSA. The 3H-GEMSA binding to enkephalin convertase in the spinal cord of these rats produced only a slight increase in KD; besides, no changes in the enzyme activity were observed. The study shows that GEMSA has a potent pharmacological action in the central nervous system. Furthermore, this effect is partly due to the influence of GEMSA on endogenous opioid peptide systems, possibly on proenkephalin A.
D000700:Analgesics; D000818:Animals; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D003292:Convulsants; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013386:Succinates / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D003292:Convulsants; D013386:Succinates; C022014:guanidinoethylmercaptosuccinic acid; D002268:Carboxypeptidases; D043423:Carboxypeptidase H