Pharmacology of new glutarimide compounds.
New glutarimide compounds were synthesized by incorporating piperidine (compounds 1 to 7), diethylamine (8 and 9), morpholine moities (10 to 13), and alkyl derivatives of 3,5 dicyanoglutarimide (14 to 20) at position -1 of the nitrogen atom. Only compounds 1 to 7 at a dose of 8 mg/kg i.p. caused hypermotility, ataxia, tachypnoea and mild tremors in mice. At higher doses (32 mg/kg i.p.), all compounds induced tonic and clonic convulsions, respiratory paralysis and death. The LD50 values of compounds 1 to 20 in mice range from 152 to 488 mg/kg i.p. and for compounds 21 to 23, the p.o. values are 484, 500 and 525 mg/kg. The relative toxicity of compounds 1 to 7 and 14 to 20 showed inverse ratio in their numbers. Basic compounds 21 to 23 at high dose levels (64 mg/kg i.p.) induced only hypnotic depression. No change was observed in organ-wise histopathological study except patchy necrosis at the site of injection of basic compounds. The CNS pharmacological studies were negative with reference to anti-convulsion, analgesic, antipyretic tests by conventional methods except at higher doses (32 or 64 mg/kg i.p.), which exhibited synergistic effects in mice and rats.
D000700:Analgesics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D001522:Behavior, Animal / Q000187:drug effects; D004048:Diethylamines / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D010881:Piperidones / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D004048:Diethylamines; D009025:Morpholines; D010880:Piperidines; D010881:Piperidones; C007864:glutarimide