N,N'-diallylbarbital potentiation of drug-induced sleep and motor incoordination

Pharmacological activities (hypnotic activity, anticonvulsant activity against pentylenetetrazol (PTZ)-induced seizures and motor incoordination) of N-allyl substituted derivatives of barbital (B) were investigated using mice. N-Monoallylbarbital (MAB) was found to possess more potent hypnotic activity [HD50 = 146(140-152)mg/kg, i.p.] and anticonvulsant activity [PTZ-ED50 = 25.1(18.1-34.8)mg/kg, i.p.] than the parent compound, barbital [HD50 = 179(153-209)mg/kg, i.p. and PTZ-ED50 = 27.7(25.5-30.1)mg/kg, i.p.]. N,N'-Diallylbarbital (DAB) was devoid of not only the hypnotic activity, but also of anticonvulsant activity and motor incoordination. The interactions of these N-allyl derivatives with various sedative-hypnotics [B, phenobarbital (PheB), amobarbital (AB), pentobarbital (PB), thiopental (TP) or diazepam (DZ)] were studied to characterize the antagonist or agonist properties of these N-allyl compounds. MAB (50-200 mg/kg, i.p.) showed a dose-dependent potentiation of B (200 mg/kg, i.p.)-induced sleep. DAB (150-300 mg/kg, i.p.) prolonged B-induced sleeping time, but its dose-response relationship was not clearly observed. Both compounds (150 mg/kg, i.p.) also significantly prolonged PheB-, AB-, PB- and TP-induced sleeping time. Further, DAB (40 mg/kg, i.p.) enhanced DZ-induced motor incoordination. These results indicate that MAB and DAB potentiate sedative-hypnotics responses in different manner, and that the mechanism of action may be due to their different effect, each other, on the central nervous system (CNS).