Abstract

After i.v. administration in mice, 5-(2-cyclohexylideneëthyl)-5-ethyl barbituric acid and the (+)-isomer of 5-(1,3-dimethylbutyl)-5-ethyl barbituric acid (DMBB) induced tonic extensor seizures preceded by brief tonic flexion. No evidence of depression preceded or accompanied these seizures. In contrast, the (—)-isomer of DMBB induced preanesthetic excitation without tonic seizures and antagonized the seizure activity of the (+)-isomer. (—)-DMBB was slightly more potent than pentobarbital as a central nervous system depressant and had an LD50 over 20 times higher than (+)-DMBB. Depressant barbiturates were more effective antagonists of barbiturate-induced convulsions than were trimethadione and diphenylhydantoin. Phenobarbital was an effective antagonist at \m=1/15\ of its neurotoxic dose 50. Barbiturates that caused preanesthetic excitation without tonic seizures produced simple depression at lower doses than those needed to elicit preanesthetic excitation. On the basis of these studies it is concluded that the depression which accompanies the seizure activity of racemic DMBB is not a necessary concomitant of barbiturate excitation and obscures the full convulsant effect.