Shimizu H, Kumasaka Y, Tanaka H, Hirose A, Nakamura M
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Jpn J Pharmacol. 1992 Mar;58(3):283-9. doi: 10.1254/jjp.58.283.
Tandospirone is a novel non-benzodiazepine compound possessing potent anxiolytic properties in a water lick conflict paradigm in rats and a high affinity for central 5-HT1A receptors. In the present study, tandospirone was evaluated for anxiolytic activity in a modified Geller-Seifter conflict paradigm in rats. Tandospirone produced significant increases in the punished responding at doses of 1.25, 2.5 and 5.0 mg/kg, i.p. or 20 mg/kg, p.o., although it decreased unpunished responding at doses of 2.5 and 5.0 mg/kg, i.p. or 20 mg/kg, p.o. Likewise, diazepam was also effective after i.p.-administration in this test, and its minimum effective dose was slightly higher than that of tandospirone. This suggests that tandospirone might be as effective in the treatment of anxiety as diazepam. The anticonflict action of tandospirone was not inhibited by Ro-15-1788, a benzodiazepine antagonist, although that of diazepam was completely inhibited. 8-OH-DPAT, a full agonist of 5-HT1A receptors, was also effective in this test with a high potency. Therefore, the possibility exists that the anticonflict action of tandospirone is related to its agonist action on 5-HT1A receptors, not on benzodiazepine receptors.
坦度螺酮是一种新型非苯二氮䓬类化合物,在大鼠水舔冲突实验模型中具有强效抗焦虑特性,且对中枢5-羟色胺1A(5-HT1A)受体具有高亲和力。在本研究中,对坦度螺酮在改良的大鼠盖勒-赛弗特冲突实验模型中的抗焦虑活性进行了评估。腹腔注射剂量为1.25、2.5和5.0mg/kg或口服剂量为20mg/kg时,坦度螺酮可使受罚反应显著增加,不过腹腔注射剂量为2.5和5.0mg/kg或口服剂量为20mg/kg时,它会使未受罚反应减少。同样,地西泮腹腔注射给药在该实验中也有效,其最小有效剂量略高于坦度螺酮。这表明坦度螺酮在治疗焦虑方面可能与地西泮一样有效。坦度螺酮的抗冲突作用未被苯二氮䓬拮抗剂Ro-15-1788抑制,而地西泮的抗冲突作用则被完全抑制。5-HT1A受体的完全激动剂8-羟基二丙胺基四氢萘(8-OH-DPAT)在该实验中也高效有效。因此,存在这样一种可能性,即坦度螺酮的抗冲突作用与其对5-HT1A受体而非苯二氮䓬受体的激动作用有关。