Effects of DN-2327, a new anxiolytic, diazepam and buspirone on exploratory activity of the rat in an elevated plus-maze.
In the present study, the effects of a new anxiolytic, DN-2327, were compared to those of diazepam and buspirone in rats in the elevated plus-maze test. Two indices of anxiety were obtained in this test: the number of entries into the open arms expressed as a percentage of the total number of arm entries and the percentage of time spent on the open arms. Both a typical anxiolytic, diazepam, at 2.5, 5 and 10 mg/kg, PO and a new anxiolytic, DN-2327, at 2.5 and 5 mg/kg, PO dose-dependently increased the two indices: the percentage of time spent on the open arms and the percentage of open-arm entries. On the other hand, pentylenetetrazol (PTZ) at 10 and 20 mg/kg, IP decreased the two indices dose dependently as did yohimbine at 1.5 and 3 mg/kg, IP. DN-2327 at 2.5 and 5 mg/kg, PO and diazepam at 5 and 10 mg/kg, PO dose dependently and significantly increased the two indices that were suppressed following administration of PTZ at 10 mg/kg, IP. The effects of both DN-2327, 5 mg/kg, PO, and diazepam, 10 mg/kg, PO, on the two indices were significantly antagonized by the benzodiazepine (BZD) receptor antagonist flumazenil, 20 mg/kg, IP. Buspirone (2.5-20 mg/kg, PO) did not affect either of the two responses but dose dependently decreased the number of rearings, although in the Vogel conflict test, the anti-conflict activity of buspirone was equipotent to that of diazepam and DN-2327 at the minimum effective dose (10 mg/kg, PO) of each drug.(ABSTRACT TRUNCATED AT 250 WORDS)
Biology Research Laboratories, Takeda Chemical Industries, Osaka, Japan.
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Wada
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Fukuda
D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology*; D002065:Buspirone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003220:Conflict, Psychological; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004597:Electroshock; D005106:Exploratory Behavior / Q000187:drug effects*; D005442:Flumazenil / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D009287:Naphthyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013141:Spiro Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D009287:Naphthyridines; D013141:Spiro Compounds; D015016:Yohimbine; D005442:Flumazenil; C060382:pazinaclone; D003975:Diazepam; D002065:Buspirone; D010433:Pentylenetetrazole