title: Attenuation of the antinociceptive action of the selective kappa-opioid receptor agonist, U-50,488H by ICS-205-930.
abstract: The antinociceptive action of s.c. administered U-50,488H was antagonized by s.c. administered ICS-205-930, a selective 5-HT3 receptor antagonist. To characterize the site of interaction, U-50,488H and ICS-205-930 were administered either intracerebroventricularly (i.c.v.) or intrathecally (i.t.). When U-50,488H was administered i.c.v., its antinociception action was antagonized by ICS-205-930 given either i.c.v. or i.t., increasing the ED50 values of U-50,488H by approximately twofold from 48 to 98 and 90 nmol/mouse, respectively. However, when U-50,488H was administered i.t., its antinociception action was not antagonized by ICS-205-930 given either i.c.v. or i.t. These findings suggest that i.c.v., but not i.t. administered U-50,488H may release serotonin both supraspinally and spinally to interact with 5-HT3 receptors to produce antinociception.
authors.affiliation: Department of Pharmacology, Medical School, University of Minnesota, Minneapolis.
authors.forename: B Y
authors.initials: BY
authors.lastname: Ho
authors.forename: A E
authors.initials: AE
authors.lastname: Takemori
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000037:antagonists & inhibitors*; D000818:Animals; D007211:Indoles / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D011759:Pyrrolidines / Q000037:antagonists & inhibitors*; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D000077526:Tropisetron
chemical_list: D000700:Analgesics; D007211:Indoles; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000077526:Tropisetron