U50,488, a highly selective kappa opioid: anticonvulsant profile in XXXX .

@entity410 @entity1510 @entity15945 @entity302 @entity35
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 @entity410 -specific; thus, U50,488 protected against supramaximal electroshock @entity410 but failed to raise the threshold of @entity15945 -induced @entity410 . 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 @entity1510 . Results indicate that U50,488 is an efficacious, long-acting anticonvulsant against supramaximal, but not chemical threshold, @entity410 in @entity35 . Furthermore, the results with @entity1510 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 @entity302 .
