Table 3

Classic antiepileptic drugs: PIs against cocaine-induced seizures and proposed mechanisms of action

Drug	PI (TD₅₀/ED₅₀)^3-a	Proposed Primary Mechanims of Action^3-b
Valproic acid	1.22	Increases GABA levels through stimulation of GABA synthesis and/or inhibition of GABA-transaminase
Clonazepam	0.90	Benzodiazepine positive GABA_Areceptor modulator
Diazepam	0.13	Benzodiazepine positive GABA_A receptor modulator
Ethosuximide	0.88	T-type Ca²⁺ channel blocker
Trimethadione	N.E.	T-type Ca²⁺channel blocker
Phenytoin	N.E.	Na⁺ channel blocker
Carbamazepine	N.E.	Na⁺ channel blocker
Primidone	N.E.	Prodrug for phenobarbital, Na⁺ channel blocker
Phenobarbital	N.E.	Barbiturate positive GABA_Areceptor modulator, Na⁺ channel blocker

N.E., lack of significant efficacy against cocaine-induced seizures.
↵3-a Protective indices from Witkin et al. (1999).
↵3-b Mechanisms of action of the drugs were cited from Rogawski and Porter, 1990; Löscher and Schmidt, 1994; Macdonald and Kelly, 1995.