title: The kappa agonists PD117302 and U50488 produce a biphasic effect on 24 hour food intake in the rat.
abstract: The effects of the selective kappa opioid receptor agonists PD117302 [(+/-)trans-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl-]benzo-[b]- thiophene-4-acetamide] and U50488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide) were investigated on food intake in non-deprived rats over a 24 hr period following subcutaneous administration. At doses of 2.5 mg/kg and 5 mg/kg, both PD117302 and U50488 initially increased food intake. Between 6-24 hr, however, PD117302 (2.5-10 mg/kg) and U50488 (2.5 mg/kg and 5 mg/kg) caused a reduction in food intake. The largest doses of PD117302 and U50488 also reduced total 24 hr food intake. The reduction in food intake produced by PD117302 (5 mg/kg) was selective, since the intake of water was not affected. It is concluded that the kappa agonists PD117302 and U50488 produce a biphasic effect on 24 hr food intake, with an initial hyperphagia followed by a decrease in food intake.
authors.affiliation: Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge, U.K.
authors.forename: G
authors.initials: G
authors.lastname: Hewson
authors.forename: R G
authors.initials: RG
authors.lastname: Hill
authors.forename: J
authors.initials: J
authors.lastname: Hughes
authors.forename: G E
authors.initials: GE
authors.lastname: Leighton
authors.forename: W D
authors.initials: WD
authors.lastname: Turner
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004435:Eating / Q000187:drug effects; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D009294:Narcotics; D011758:Pyrroles; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D013876:Thiophenes; C054718:PD 117302; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer