Analgesic and convulsant effects of guanidinoethylmercaptosuccinic acid (GEMSA)--a potent enkephalin convertase inhibitor.

Abstract

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.

• Authors: B Przewlocka, M Dziedzicka, J Silberring, W Lason
• Journal: Neuropeptides (Neuropeptides) 1986 Nov-Dec Vol. 8 Issue 4 Pg. 359-65 ISSN: 0143-4179 [Print] Netherlands
• PMID: 3102992 (Publication Type: Journal Article)

Chemical References

• Analgesics
• Convulsants
• Succinates
• guanidinoethylmercaptosuccinic acid
• Carboxypeptidases
• Carboxypeptidase H

Topics

• Analgesics
• Animals
• Carboxypeptidase H
• Carboxypeptidases (antagonists & inhibitors)
• Cerebral Ventricles (drug effects, physiology)
• Convulsants
• Injections, Intraventricular
• Male
• Motor Activity (drug effects)
• Rats
• Rats, Inbred Strains
• Succinates (administration & dosage, pharmacology)