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 mice at doses higher than 20 mg/kg. Animals presenting seizures showed a marked preconvulsive phase followed by short duration hind limb myoclonus, respiratory spasms, and death. The lethal nature of ricinine seizures is also pointed out as a good model to study the events causing death in clonic seizures, particularly those related to respiratory spasms, which are also observed in some types of human epilepsy. The behavioral signs of ricinine-elicited seizures are accompanied by electrographic alterations more evident during the preconvulsive phase in the cerebral cortex and more intense during the ictal phase both in the cortex and in the hippocampus. The ricinine-elicited seizures may be inhibited by diazepam but not by phenobarbital, phenytoin, or ethosuximide. Micromolar concentrations of ricinine cause a small decrease in the binding of [3H]-flunitrazepam to cerebral cortex membranes, but do not alter the binding of other radioligands to AMPA, 5-HT(1A), muscarinic, and alpha(1)-adrenergic receptors. Although ricinine presents a cyanide radical, only higher doses of ricinine (4 mM) caused a small impairment of mitochondrial respiration. These results suggest that the mechanism of action of ricinine probably involves the benzodiazepine site in the GABA(A) receptor. This may represent a new mechanism of drug-elicited seizures that may contribute to a better understanding of epilepsy and to new therapeutic approaches to this disease.
Ferraz
A C
AC
Laboratório de Fisiologia e Farmacologia do SNC, Departamento de Fisiologia e Dep. Farmacologia, Univ. Fed. Paraná, C.P. 19.031, 81. 531-990, Curitiba, PR, Brazil.
Pereira
L F
LF
Ribeiro
R L
RL
Wolfman
C
C
Medina
J H
JH
Scorza
F A
FA
Santos
N F
NF
Cavalheiro
E A
EA
Da Cunha
C
C
D000470:Alkaloids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D013956:Antithyroid Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D003292:Convulsants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011728:Pyridones; D011869:Radioligand Assay; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced* / Q000523:psychology
D000470:Alkaloids; D000927:Anticonvulsants; D013956:Antithyroid Agents; D003292:Convulsants; D011728:Pyridones; D017981:Receptors, Neurotransmitter; C019550:ricinine