Sanders K H, Beller K D, Bischler P, Kolassa N
Department of Pharmacology, Byk Gulden Pharmaceuticals, Konstanz, Federal Republic of Germany.
J Hypertens Suppl. 1988 Dec;6(2):S65-8.
The alpha-adrenoceptor antagonist urapidil influences central cardiovascular regulation, and this effect is unrelated to alpha-adrenoceptors. Since urapidil has appreciable affinity and selectivity for serotonin-1A (5HT1A) receptors, the activity of urapidil at these sites may be relevant for the centrally mediated component of its antihypertensive action. The latter hypothesis was tested by analysing the influence of the 5HT1A receptor antagonist spiroxatrine on the hypotensive response to urapidil, in comparison with the influence on the hypotensive response to the 5HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin). Anaesthetized cats were thoracotomized and artificially ventilated. Blood pressure was monitored in the descending aorta, and the drugs were injected into the vertebral artery. Spiroxatrine (0.1-3.0 nmol/kg) shifted the cumulative dose response curve (blood pressure reduction) of urapidil (3-20 nmol/kg) and of 8-OH-DPAT (0.01-0.1 nmol/kg) to the right, suggesting competitive antagonism. The results support the hypothesis that the effects of urapidil on central cardiovascular regulation and at least part of the hypotensive effects are due to 5HT1A receptor stimulation.
α-肾上腺素能受体拮抗剂乌拉地尔影响中枢心血管调节，且这种作用与α-肾上腺素能受体无关。由于乌拉地尔对5-羟色胺-1A（5HT1A）受体具有显著的亲和力和选择性，其在这些位点的活性可能与其降压作用的中枢介导成分相关。通过分析5HT1A受体拮抗剂螺沙群对乌拉地尔降压反应的影响，并与对5HT1A受体激动剂8-OH-DPAT（8-羟基-2-[二正丙基氨基]四氢萘）降压反应的影响进行比较，对后一种假设进行了验证。将麻醉的猫开胸并进行人工通气。在降主动脉监测血压，并将药物注入椎动脉。螺沙群（0.1 - 3.0 nmol/kg）使乌拉地尔（3 - 20 nmol/kg）和8-OH-DPAT（0.01 - 0.1 nmol/kg）的累积剂量反应曲线（血压降低）右移，提示竞争性拮抗作用。结果支持以下假设，即乌拉地尔对中枢心血管调节的作用以及至少部分降压作用是由于5HT1A受体激动所致。
