Single application of a CB1 receptor antagonist rapidly following head injury prevents long-term hyperexcitability in a rat model.
Effective prophylaxis for post-traumatic epilepsy currently does not exist, and clinical trials using anticonvulsant drugs have yielded no long-term antiepileptogenic effects. We report that a single, rapid post-traumatic application of the proconvulsant cannabinoid type-1 (CB1) receptor antagonist SR141716A (Rimonabant-Acomplia) abolishes the long-term increase in seizure susceptibility caused by head injury in rats. These results indicate that, paradoxically, a seizure-enhancing drug may disrupt the epileptogenic process if applied within a short therapeutic time window.
Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697-1280, United States.
Julio
J
Echegoyen
Caren
C
Armstrong
Robert J
RJ
Morgan
Ivan
I
Soltesz
D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use; D006259:Craniocerebral Trauma / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004834:Epilepsy, Post-Traumatic / Q000209:etiology / Q000517:prevention & control*; D010424:Pentobarbital / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant
D000927:Anticonvulsants; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D010424:Pentobarbital; D000077285:Rimonabant