Effects of 5-HT and alpha 1 adrenoceptor antagonists on kappa opioid-induced sedation.
The kappa opioid agonists PD-117302 and U-50488 were found to produce dose-dependent reductions in spontaneous locomotor activity in mice. The magnitude of the response to a given dose of each kappa agonist was found to be clearly potentiated by pretreating the animals with either ketanserin (1 mg/kg) or prazosin (0.5 mg/kg). Pretreatment with the selective 5-HT2 receptor antagonist ritanserin given at a high dose (1 mg/kg), the nonselective 5-HT antagonist methysergide or the 5-HT synthesis inhibitor parachlorophenylalanine did not alter the magnitude of the response to the kappa agonist. These results suggest that 5-HT systems are not involved in the sedative effects of kappa opioid agonists and that the potentiating effect seen in animals pretreated with ketanserin is due to the alpha 1 blocking properties of this compound since the effect was mimicked by the alpha 1 antagonist prazosin.
Leighton
G E
GE
Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge.
Hill
R G
RG
Hughes
J
J
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000502:physiology*; D012701:Serotonin / Q000032:analysis; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D011758:Pyrroles; D011759:Pyrrolidines; D011957:Receptors, Opioid; D012702:Serotonin Antagonists; D013876:Thiophenes; C054718:PD 117302; D012701:Serotonin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D011224:Prazosin