Central effects of N-substituted derivatives of 2,6-dioxopiperidine in mice

Pharmacological activities of N-allyl, N-benzyl and N-o-xylyl derivatives of both 2,6-dioxopiperidine (DOP = glutarimide) and 4-ethyl-4-methyl-2,6-dioxopiperidine [bemegride(BG)] were studied in mice. Convulsant activity, hypnotic activity, anticonvulsant activity, acute toxicity and interactions with some hypnotics were used as pharmacological indexes. N-Benzyl-2,6-dioxopiperidine (ByDOP) and N-o-xylyl-2,6-dioxopiperidine (o-XyDOP) exhibited some hypnotic activity. N-Allyl-2,6-dioxopiperidine (ADOP), ByDOP and o-XyDOP prolonged the pentobarbital (PB)-induced sleep by 2.5-, 9- and 4-fold, respectively, as compared with the control at a dose of 80 mg/kg, i.p. On the other hand, N-allylbemegride (ABG) exhibited convulsant activity at a high dose. N-Benzylbemegride (ByBG) and N-o-xylylbemegride (o-XyBG) also showed some hypnotic and anticonvulsant activities. BG (20 mg/kg, i.p.) shortened the amobarbital (AB)- and thiopental (TP)-induced sleep, whereas ABG (80 mg/kg, i.p.) significantly shortened only the barbital (B)-induced sleep, in spite of showing with 20 and 80 mg/kg, i.p. the prolonging effect on the AB- and PB-induced sleep. At a dose of 80 mg/kg, i.p., ByBG significantly prolonged the phenobarbital (PheB)-, AB-, PB-, TP- and glutethimide (GI)-induced sleep, and o-XyBG also showed the prolonging effect on the PheB-, AB-, TP- and GI-induced sleep. These results indicate that ByDOP and o-XyDOP possess some central depressant effect, ABG has antagonistic effect on the B-induced sleep and that substitution of aromatic groups on the N position of BG reduces the convulsant activity but increases the depressant activity.