Vayssettes-Courchay C, Bouysset F, Verbeuren T J, Laubie M, Schmitt H
Institut de Recherches Servier, Suresnes, France.
Eur J Pharmacol. 1990 Aug 2;184(1):75-85. doi: 10.1016/0014-2999(90)90668-v.
Quipazine (0.5-2 mg/kg i.v.) produced transient hypotension and bradycardia followed by sustained hypertension and variable effects on heart rate in anaesthetized rats. The hypotension, bradycardia and sympatho-inhibitory effects of quipazine were attenuated by bivagotomy. In bivagotomized rats, the hypertension produced by quipazine was not modified by hexamethonium or prazosin but was abolished by ritanserin (1 mg/kg i.v.). In ritanserin-treated rats, section of the carotid sinus nerves and vagus nerves or ICS 205.930 (0.1 mg/kg i.v.) abolished the hypotensive, bradycardic and sympatho-inhibitory effects of quipazine; the action of quipazine was not reproducible in these rats. Quipazine also inhibited the Bezold-Jarish reflex elicited by 5-HT (20 micrograms/kg i.v.). In ICS 205.930-treated rats, the hypertension evoked by quipazine was associated with a reduction in splanchnic nerve activity due to stimulation of baroreceptors. The renin-angiotensin system is not involved in the hypertensive response. The increase in heart rate produced by quipazine in bivagotomized rats was reduced by ritanserin and tertatolol (0.1 mg/kg i.v.) and abolished by a combination of both drugs. We conclude that the bradycardic and sympatho-inhibitory effects of quipazine result from activation of 5-HT3 receptors located in the cardiopulmonary area and of carotid body chemoreceptors. The hypertension and tachycardia are mediated by vascular and myocardial 5-HT2 receptors. No evidence was obtained for a central sympatho-excitatory effect.
喹哌嗪（静脉注射0.5 - 2毫克/千克）可使麻醉大鼠出现短暂性低血压和心动过缓，随后出现持续性高血压，并对心率产生不同影响。喹哌嗪的低血压、心动过缓和交感神经抑制作用可被双侧迷走神经切断术减弱。在双侧迷走神经切断的大鼠中，喹哌嗪引起的高血压不受六甲铵或哌唑嗪的影响，但可被利坦色林（静脉注射1毫克/千克）消除。在利坦色林处理的大鼠中，切断颈动脉窦神经和迷走神经或注射ICS 205.930（静脉注射0.1毫克/千克）可消除喹哌嗪的降压、心动过缓和交感神经抑制作用；喹哌嗪在这些大鼠中不再产生作用。喹哌嗪还可抑制5 - 羟色胺（静脉注射20微克/千克）引发的贝佐尔德 - 雅里什反射。在ICS 205.930处理的大鼠中，喹哌嗪引起的高血压与由于压力感受器刺激导致的内脏神经活动减少有关。肾素 - 血管紧张素系统不参与高血压反应。喹哌嗪在双侧迷走神经切断的大鼠中引起的心率增加可被利坦色林和特他洛尔（静脉注射0.1毫克/千克）降低，并被两种药物联合使用所消除。我们得出结论，喹哌嗪的心动过缓和交感神经抑制作用是由位于心肺区域的5 - HT3受体和颈动脉体化学感受器的激活引起的。高血压和心动过速由血管和心肌的5 - HT2受体介导。未获得中枢交感神经兴奋作用的证据。
