ly-53857 and pirenperone

The kappa opioid, U50,488, was examined alone and in combination with the 5HT2 antagonists, ketanserin, pirenperone and LY 53857. Squirrel monkeys responded under a shock titration procedure in which shock intensity increased every 15 s from 0.01 to 2.0 mA in 30 steps. Five responses terminated the shock for 15 s, after which the shock resumed at the next lower intensity. The level at which the monkeys kept the shock 50% of the time (median shock level/MSL) was determined. U50,488 alone produced dose-dependent increases in median shock level whereas none of the 5-HT2 antagonists altered responding under this procedure. When ketanserin (0.032-5.6 mg/kg) was administered in combination with U50,488, very high doses of ketanserin (3.2-5.6 mg/kg) shifted the U50,488 dose-effect curve to the left. Neither pirenperone (0.032-10.0 micrograms/kg) nor LY53857 (0.01-0.32 mg/kg) altered the U50,488 dose-effect curve in any monkey. Taken together, these data do not support a role for the 5-HT2 system in kappa-induced antinociception in the primate.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Dose-Response Relationship, Drug; Drug Interactions; Electric Stimulation; Ergolines; Ketanserin; Male; Piperidines; Pyrrolidines; Receptors, Opioid, kappa; Saimiri; Serotonin Antagonists

The present studies have attempted to evaluate the role of 5-HT2 receptors in the regulation of sexual behavior of male rats by determining the effects of 5-HT2 receptor antagonists, pirenperone, LY53857 and LY281067, and a 5-HT2 receptor agonist, DOI. The administration of 1 mg/kg s.c. pirenperone produced a total suppression of ejaculatory response and lower doses had no effect. However, the administration 0.1 mg/kg s.c. of either LY53857 or LY281067 restored ejaculatory capacity to rats that were unable to ejaculate and produced significant decreases in ejaculatory latency in rats with full sexual capacity. Although all of these agents are 5-HT2 antagonists, LY53857 and LY281067 lack the additional monoaminergic activity of pirenperone. Since the effects of pirenperone were opposite from the effects of the selective 5-HT2 antagonists, the suppressive effects of this agent were probably related to its other monoaminergic activity e.g. alpha 1 antagonist activity. This proposal was supported by the observation that the administration of prazosin, an alpha 1 antagonist, significantly increased ejaculatory latency and suppressed the stimulatory effects of LY53857. In contrast to the stimulatory effects of the selective 5-HT2 antagonists, the administration of DOI, resulted in a suppression of sexual performance, which was blocked by pretreatment with LY53857.

Topics: Amphetamines; Animals; Copulation; Ejaculation; Ergolines; Female; Lysergic Acid; Male; Piperidines; Prazosin; Rats; Rats, Inbred Strains; Receptors, Serotonin; Serotonin Antagonists; Sexual Behavior, Animal