Chow C M, Winder C, Read D J
J Appl Physiol (1985). 1986 Feb;60(2):370-5. doi: 10.1152/jappl.1986.60.2.370.
Ventilatory and carotid body responses to hypoxia have been related to the endogenous release of dopamine by use of the antagonist drug haloperidol. The published studies have produced conflicting data for ventilation. However, antagonist drugs can act at multiple anatomical sites, on multiple pharmacological receptors, often at different dosages, and have nonspecific actions at high dosage. For these reasons, we have undertaken a systematic study of haloperidol dose-response curves with particular emphasis on the lowest possible concentrations of drug. In five cats anesthetized with pentobarbital sodium (30-35 mg/kg), single- or few-fiber afferent recordings of the carotid body showed that haloperidol increased the discharge during both basal and asphyxic conditions, the increments being proportional to haloperidol dosage (0.1-1,000 micrograms/kg). Increments of ventilation were also produced, these increments increasing only over the lower range of dosage; at the highest haloperidol dosage, the dose response showed a tendency to plateau or inflect downward, suggesting the appearance of an opposing inhibitory mechanism.
通过使用拮抗剂药物氟哌啶醇,已将通气和颈动脉体对缺氧的反应与多巴胺的内源性释放联系起来。已发表的研究得出了关于通气的相互矛盾的数据。然而,拮抗剂药物可作用于多个解剖部位、多种药理受体,且常常剂量不同,高剂量时还具有非特异性作用。基于这些原因,我们对氟哌啶醇剂量反应曲线进行了系统研究,特别强调尽可能低的药物浓度。在用戊巴比妥钠(30 - 35毫克/千克)麻醉的五只猫中,对颈动脉体进行单纤维或少数纤维传入记录显示,氟哌啶醇在基础和窒息条件下均增加了放电,增加量与氟哌啶醇剂量(0.1 - 1000微克/千克)成比例。通气也出现了增加,这些增加仅在较低剂量范围内增加;在最高氟哌啶醇剂量时,剂量反应显示出趋于平稳或向下弯曲的趋势,提示出现了一种相反的抑制机制。