Article date: 1991/7/1
PubMed ID: 1657321
Journal name: Brain research bulletin (ISSN: 0361-9230)
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.
Author List: Bansinath M, Ramabadran K, Turndorf H, Shukla V K
Publication Types: Journal Article
Substances mentioned in the article: Analgesics; Benzeneacetamides; Benzomorphans; Convulsants; Narcotic Antagonists; Narcotics; Pyrroles; Pyrrolidines; Receptors, Opioid; Receptors, Opioid, kappa; Thiophenes; PD 117302; Muscimol; Naloxone; MR 2266; 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Ketamine; Dizocilpine Maleate; Baclofen; U 69593;
Mesh terms: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics/pharmacology; Animals; Baclofen/pharmacology; Benzeneacetamides; Benzomorphans/pharmacology; Cerebral Ventricles/drug effects; Convulsants/pharmacology; Dizocilpine Maleate/pharmacology; Injections, Intraventricular; Ketamine/pharmacology; Mice; Mice, Inbred Strains; Muscimol/pharmacology; Naloxone/pharmacology; Narcotic Antagonists/pharmacology; Narcotics/pharmacology; Pyrroles/pharmacology; Pyrrolidines/pharmacology; Receptors, Opioid/drug effects; Receptors, Opioid, kappa; Seizures/chemically induced; Stereoisomerism; Thiophenes/pharmacology;