Ricinine-elicited seizures: A novel chemical model of convulsive seizures

The present investigation introduces ricinine-elicited seizures as a novel chemical model of convulsive seizure. Ricinine, a neutral alkaloid obtained from the plant Ricinus communis, induces seizures when administered to mic e at doses higher than 20 mg/kg. Animals presenting sei zures showed a mark ed preconvulsive phase followed by short duration hind limb myoclonus: resp iratory spasms, and death. The lethal nature of ricinine seizures is also p ointed out as a good model to study the events causing death in clonic seiz ures, particularly those related to respiratory spasms, which are also obse rved in some types of human epilepsy. The behavioral signs of ricinine-elic ited seizures are accompanied by electrographic alterations more evident du ring the preconvulsive phase in the cerebral cortex and more intense during the ictal phase both in the cortex and in the hippocampus. The ricinine-el icited seizures may be inhibited by diazepam but not by phenobarbital, phen ytoin, or ethosuximide. Micromolar concentrations of ricinine cause a small decrease in the binding of [H-3]-flunitrazepam to cerebral cortex membrane s, but do not alter the binding of other radioligands to AMPA, 5-HT1A, musc arinic, and alpha(1)-adrenergic receptors. Although ricinine presents a cya nide radical, only higher doses of ricinine (4 mM) caused a small impairmen t of mitochondrial respiration. These results suggest that the mechanism of action of ricinine probably involves the benzodiazepine site in the GABA, receptor. This may represent a new mechanism of drug-elicited seizures that may contribute to a better understanding of epilepsy and to new therapeuti c approaches to this disease. (C) 2000 Elsevier Science Inc.