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.
Tateoka
Y
Y
Shinshin Chemical Industries Ltd., Toyama, Japan.
Kimura
T
T
Kamiyama
H
H
Watanabe
K
K
Yamamoto
I
I
Ho
I K
IK
D000818:Animals; D000927:Anticonvulsants; D001534:Bemegride / Q000031:analogs & derivatives / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects*; D003292:Convulsants; D006993:Hypnotics and Sedatives; D008297:Male; D051379:Mice; D010880:Piperidines / Q000494:pharmacology*; D010881:Piperidones / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D003292:Convulsants; D006993:Hypnotics and Sedatives; D010880:Piperidines; D010881:Piperidones; D001534:Bemegride; C007864:glutarimide