Intracerebroventricular administration of kappa-agonists induces convulsions in mice.
Intracerebroventricular (ICV) administration of kappa-agonists (PD 117302, U-50488H and U-69593) induced convulsions in a dose-related manner in mice. The dose at which 50% of animals convulsed (CD50) was in nmol ranges for all opioids. Among the opioids used, PD 117302 was the most potent convulsant. ICV administration of either vehicle alone or U-53445E, a non-kappa-opioid (+) enantiomer of U-50488H did not induce convulsions. The convulsive response of kappa-agonists was differentially susceptible for antagonism by naloxone and/or MR 2266. Collectively, these findings support the view that convulsions induced by kappa-agonists in mice involve stereospecific opioid receptor mechanisms. Furthermore, the convulsant effect of kappa-agonists could not be modified by pretreatment with MK-801, ketamine, muscimol or baclofen. It is concluded that kappa-opioid but not NMDA or GABA receptor mechanisms are involved in convulsions induced by kappa-agonists. These results are the first experimental evidence implicating stereospecific kappa-receptor mechanisms in opioid-induced convulsions in mice.
Bansinath
M
M
Department of Anesthesiology, School of Medicine, New York University Medical Center, NY 10016.
Ramabadran
K
K
Turndorf
H
H
Shukla
V K
VK
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D044482:Benzeneacetamides; D001575:Benzomorphans / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D003292:Convulsants / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D007276:Injections, Intraventricular; D007649:Ketamine / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D013237:Stereoisomerism; D013876:Thiophenes / Q000494:pharmacology
D000700:Analgesics; D044482:Benzeneacetamides; D001575:Benzomorphans; D003292:Convulsants; D009292:Narcotic Antagonists; D009294:Narcotics; D011758:Pyrroles; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D013876:Thiophenes; C054718:PD 117302; D009118:Muscimol; D009270:Naloxone; C027247:MR 2266; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D007649:Ketamine; D016291:Dizocilpine Maleate; D001418:Baclofen; C045444:U 69593