Castillo C, Bobadilla R A, Ibarra M, Castillo E F, Hong E
Departamento de Fisiología y Farmacología de la Escuela Superior de Medicina IPN, México, D.F.
Arch Med Res. 1995 Autumn;26(3):251-5.
The intention of this study was to supply additional information about direct effects of the 5-HT1A receptor agonist indorenate on the arterial blood pressure. The effects of indorenate were compared with those of buspirone and ipsapirone (all selective 5-HT1A agonists) on the blood pressure of pithed rats. These compounds increased the blood pressure in a dose-dependent fashion. The effects of either ipsapirone or buspirone were clearly inhibited with 100 micrograms/kg of prazosin (selective alpha 1-adrenoceptor antagonist), whereas 1 mg/kg of this blocker elicited only a mild inhibition of the pressor effect of indorenate. Pindolol (100 micrograms/kg; a beta-adrenoceptor and 5-HT1 receptor blocker) was unable to modify the effects of all the 5-HT1A agonists tested. In addition, the 5-HT2 receptor and weak alpha 1-adrenoceptor blocker ketanserin (10-100 micrograms/kg) antagonized the pressor effect of indorenate. Nevertheless, only a mild inhibition was observed in the case of both ipsapirone and buspirone. On the other hand, the latter drugs diminished the blood pressure of pithed rats intravenously infused with norepinephrine, but indorenate was inactive. However, in rats infused with quipazine, all the 5-HT1A agonists failed to reduce blood pressure. These results indicate that buspirone and ipsapirone behaved as partial alpha 1-adrenoceptor agonists. Furthermore, the results show that indorenate-elicited pressor effects are probably due to stimulation of 5-HT2 receptors. Thus, unlike ipsapirone and buspirone, indorenate did not show conclusively activity related with alpha 1-adrenoceptors.
本研究旨在提供关于5-羟色胺1A（5-HT1A）受体激动剂茚达雷酯对动脉血压直接作用的更多信息。将茚达雷酯的作用与丁螺环酮和伊沙匹隆（均为选择性5-HT1A激动剂）对脊髓损伤大鼠血压的作用进行比较。这些化合物以剂量依赖性方式升高血压。100微克/千克的哌唑嗪（选择性α1-肾上腺素能受体拮抗剂）可明显抑制伊沙匹隆或丁螺环酮的作用，而1毫克/千克的该阻滞剂仅对茚达雷酯的升压作用产生轻微抑制。吲哚洛尔（100微克/千克；β-肾上腺素能受体和5-HT1受体阻滞剂）无法改变所测试的所有5-HT1A激动剂的作用。此外，5-HT2受体和弱α1-肾上腺素能受体阻滞剂酮色林（10 - 100微克/千克）可拮抗茚达雷酯的升压作用。然而，在伊沙匹隆和丁螺环酮的情况下仅观察到轻微抑制。另一方面，后两种药物可降低静脉注射去甲肾上腺素的脊髓损伤大鼠的血压，但茚达雷酯无此作用。然而，在注射喹哌嗪的大鼠中，所有5-HT1A激动剂均未能降低血压。这些结果表明，丁螺环酮和伊沙匹隆表现为部分α1-肾上腺素能受体激动剂。此外，结果表明茚达雷酯引起的升压作用可能是由于对5-HT2受体的刺激。因此，与伊沙匹隆和丁螺环酮不同，茚达雷酯并未明确显示出与α1-肾上腺素能受体相关的活性。
