Wada T, Fukuda N
Biology Research Laboratories, Takeda Chemical Industries, Osaka, Japan.
Psychopharmacology (Berl). 1991;104(4):444-50. doi: 10.1007/BF02245647.
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)
在本研究中,在高架十字迷宫试验中,将一种新型抗焦虑药DN - 2327与地西泮和丁螺环酮对大鼠的作用进行了比较。该试验获得了两个焦虑指标:进入开放臂的次数占总臂进入次数的百分比以及在开放臂上花费的时间百分比。典型抗焦虑药地西泮,经口给予2.5、5和10mg/kg,以及新型抗焦虑药DN - 2327,经口给予2.5和5mg/kg,均剂量依赖性地增加了两个指标:在开放臂上花费的时间百分比和开放臂进入次数百分比。另一方面,腹腔注射10和20mg/kg的戊四氮(PTZ)以及腹腔注射1.5和3mg/kg的育亨宾剂量依赖性地降低了这两个指标。经口给予2.5和5mg/kg的DN - 2327以及经口给予5和10mg/kg的地西泮剂量依赖性且显著地增加了腹腔注射10mg/kg PTZ后被抑制的两个指标。经口给予5mg/kg的DN - 2327和经口给予10mg/kg的地西泮对这两个指标的作用均被腹腔注射20mg/kg的苯二氮䓬(BZD)受体拮抗剂氟马西尼显著拮抗。丁螺环酮(经口给予2.5 - 20mg/kg)对这两个反应均无影响,但剂量依赖性地减少了直立次数,尽管在Vogel冲突试验中,丁螺环酮在每种药物的最小有效剂量(经口给予10mg/kg)下的抗冲突活性与地西泮和DN - 2327相当。(摘要截短于250字)