Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 237 (1), 49-53

U50,488, a Highly Selective Kappa Opioid: Anticonvulsant Profile in Rats

  • PMID: 3007743

U50,488, a Highly Selective Kappa Opioid: Anticonvulsant Profile in Rats

F C Tortella et al. J Pharmacol Exp Ther.

Abstract

Subcutaneous or i.c.v. administration of U50,488, a highly selective kappa opioid agonist, resulted in a dose-and time-dependent anticonvulsant action in rats. The anticonvulsant effect was seizure-specific; thus, U50,488 protected against supramaximal electroshock seizures but failed to raise the threshold of flurothyl-induced convulsions. The ED50 for s.c. U50,488 was 8.6 mg/kg, with a duration of action longer than 8 hr. In contrast, the ED50 for i.c.v. U50,488 was 103.8 micrograms, lasting approximately 1 hr. The anticonvulsant effect of U50,488 was partially antagonized by high (10.0 mg/kg), but not low (1.0 mg/kg), doses of s.c. administered naloxone. Results indicate that U50,488 is an efficacious, long-acting anticonvulsant against supramaximal, but not chemical threshold, seizures in rats. Furthermore, the results with naloxone suggest that this effect of U50,488 is mediated by non-mu (probably kappa) binding sites. This structurally novel nonpeptide opioid may offer new insights into the development of therapeutically effective agents in the treatment of grand mal or partial epilepsies.

Similar articles

See all similar articles

Cited by 13 PubMed Central articles

See all "Cited by" articles

LinkOut - more resources

Feedback