Chronic pharmacological activities of the novel anxiolytic beta-carboline abecarnil in rats.
Abecarnil, a novel beta-carboline anxiolytic, has been shown to possess potent anxiolytic and anticonvulsant activities with weak or no sedative and ataxic effects in relevant animal models. In the present study, anxiolytic, anticonvulsant and amnesic effects of abecarnil after single and repeated treatments in rats were compared with those of diazepam. Both abecarnil (0.52-10 mg/kg, p.o.) and diazepam (20 and 50 mg/kg, p.o.) exhibited significant anticonflict effects in the water-lick test. Neither abecarnil (5 mg/kg, p.o.) nor diazepam (50 mg/kg, p.o.) produced any tolerance to anticonflict effects after 14 days of repeated treatment. Both abecarnil (5-50 mg/kg, p.o.) and diazepam (20 and 50 mg/kg, p.o.) exhibited significant anticonvulsant effects against pentylenetetrazol-induced seizure. The anticonvulsant effects of abecarnil (5 mg/kg, p.o.) were not attenuated during 14 days of repeated treatment, but diazepam (20 and 50 mg/kg, p.o.) produced tolerance to anticonvulsant effects after 5 days of repeated treatment. In the three-panel runway task, abecarnil at 5 mg/kg, p.o. impaired only working memory, but diazepam at 20 mg/kg, p.o. impaired working memory and at 50 mg/kg, p.o. markedly impaired reference and working memories. The amnesic effects of abecarnil disappeared rapidly within 2 to 3 days of repeated treatment, whereas that of diazepam decreased rapidly but persisted during 14 days of repeated treatment. Thus, chronic abecarnil was found to exhibit persistent anxiolytic and anticonvulsant effects without any amnesic effects, in contrast to chronic diazepam.
Ozawa
M
M
Research Department, Nihon Schering K. K., Osaka, Japan.
Sugimachi
K
K
Nakada-Kometani
Y
Y
Akai
T
T
Yamaguchi
M
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002243:Carbolines / Q000494:pharmacology* / Q000627:therapeutic use; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use; D004327:Drinking Behavior / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D010433:Pentylenetetrazole / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy
D014151:Anti-Anxiety Agents; D002243:Carbolines; C062769:abecarnil; D003975:Diazepam; D010433:Pentylenetetrazole