Potentiating effects of N1,N3-diallyluracil, N1,N3-diallylthymine and N1,N3-diallyl-6-methyluracil on pentobarbital-induced sleep and diazepam-induced motor incoordination.

N-Allyl derivatives of uracil (U), thymine (T) and 6-methyluracil (6-MU) were prepared, and their pharmacological activities (hypnotic activity and anticonvulsant activity against pentylenetetrazol (PTZ)-induced seizures) and interactions with three sedative-hypnotics [pentobarbital (PB), barbital (B) and diazepam (DZ)] were investigated in mice. AO,N3-Diallyluracil (DAU) alone exhibited hypnotic and anticonvulsant activities. None of the other allyl derivatives showed both pharmacological activities. As regards interactions, most of the compounds tested prolonged PBinduced sleep at either 80 or 160 mg/kg, i.p. Further, U, T, and 6-MU (160 mg/kg, i.p.) also prolonged the PB-induced sleeping time. DAU showed a prolonging effect on PB-induced sleep when given by intracerebroventricular (i.c.v.) injection. DAU, AO,N3-diallylthymine (DAT) and N1-monoallyluracil (AO-MAU) significantly prolonged the B-induced sleeping time at a dose of 160 mg/kg, i.p. Further, DAU and DAT (40 mg/kg, i.p.) enhanced DZ-induced motor incoordination. These results indicate that U and related compounds possess central nervous system (CNS)depressant effects and DAU is the most potent among the N-allyl derivatives tested.