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.