氮杂螺环酮对中缝背核5-羟色胺1A神经元的影响。

The effects of azapirones on serotonin1A neurons of the dorsal raphe.

Matheson G K, Pfeifer D M, Weiberg M B, Michel C

Neurobiology Laboratory, Indiana University, School of Medicine, Evansville 47714.

Gen Pharmacol. 1994 Jul;25(4):675-83. doi: 10.1016/0306-3623(94)90245-3.

Abstract

The effects of buspirone, gepirone, ipsapirone and tandospirone on spontaneously discharging serotonergic neurons of the dorsal raphe were determined under the same experimental conditions. 2. Buspirone, gepirone, ipsapirone and tandospirone were equally efficacious and acted in a dose-dependent manner to totally inhibit the spontaneous activity of serotonergic neurons. 3. Based on their effects six min after administration (i.p.), their ED50 values were: buspirone, 134 micrograms/kg; ipsapirone, 220 micrograms/kg; gepirone, 225 micrograms/kg; tandospirone, 198 micrograms/kg. 4. The similarity of these ED50 data suggest that they share a similar chemical structure that binds to the 5-HT1A receptor, most likely it is "N-C-C-C-C-N" aliphatic backbone. 5. Buspirone and tandospirone required 4 or more min to totally block the spontaneous activity, while gepirone and ipsapirone blocked it in 3 min. 6. The dose-response curves from buspirone and tandospirone demonstrated enough dissimilarity to the dose-response curves from gepirone and ipsapirone to suggest differences in their rates of absorption, and/or differences in the production of active and inactive metabolites.

摘要

在相同实验条件下，测定了丁螺环酮、吉哌隆、伊沙匹隆和坦度螺酮对中缝背核自发放电的5-羟色胺能神经元的影响。2. 丁螺环酮、吉哌隆、伊沙匹隆和坦度螺酮具有同等效力，并呈剂量依赖性地完全抑制5-羟色胺能神经元的自发活动。3. 根据腹腔注射给药6分钟后的效应，它们的半数有效剂量（ED50）值分别为：丁螺环酮，134微克/千克；伊沙匹隆，220微克/千克；吉哌隆，225微克/千克；坦度螺酮，198微克/千克。4. 这些ED50数据的相似性表明它们具有相似的化学结构，可与5-HT1A受体结合，最有可能的是“N-C-C-C-C-N”脂肪族主链。5. 丁螺环酮和坦度螺酮需要4分钟或更长时间才能完全阻断自发活动，而吉哌隆和伊沙匹隆在3分钟内即可阻断。6. 丁螺环酮和坦度螺酮的剂量反应曲线与吉哌隆和伊沙匹隆的剂量反应曲线有足够差异，表明它们在吸收速率和/或活性及非活性代谢产物生成方面存在差异。