Garner S J, Eldridge F L, Wagner P G, Dowell R T
Department of Medicine, University of North Carolina, Chapel Hill 27599.
Am Rev Respir Dis. 1989 Apr;139(4):946-50. doi: 10.1164/ajrccm/139.4.946.
The recently released drug buspirone is an anxiolytic agent that appears not to have the sedating effects of barbiturates and benzodiazepines, both known to have respiratory depressant effects. Because of its increasing clinical use, we desired to study the effects of buspirone on respiratory control. We therefore determined central neural respiratory responses, measured from phrenic nerve activity, after intravenous administration in paralyzed, vagotomized, and glomectomized cats whose end-tidal PCO2 and body temperature were kept constant. The responses were compared to the effects of the sedating tranquilizer diazepam. Buspirone had a dose-dependent stimulatory effect on respiratory output primarily through an increase of tidal activity but with an increase of frequency in some animals. Associated with this was a shift of the apneic threshold to a lower level of PCO2 without a change of slope or shape of the CO2 response curve. In contrast, diazepam led to a depression of respiration and a shift of the apneic threshold to a higher PCO2. The findings indicate that buspirone does not have the typical neural respiratory depressant actions of diazepam but instead stimulates respiration. Although the findings will need to be shown to apply to human beings, they suggest that buspirone may be a useful drug to treat anxiety in patients without causing undesirable respiratory depression.
最近上市的药物丁螺环酮是一种抗焦虑药,它似乎没有巴比妥类药物和苯二氮䓬类药物的镇静作用,而后两者都已知具有呼吸抑制作用。由于其临床应用日益广泛,我们希望研究丁螺环酮对呼吸控制的影响。因此,我们在潮末二氧化碳分压(PCO2)和体温保持恒定的麻痹、迷走神经切断和肾小球切除的猫静脉注射后,根据膈神经活动测定了中枢神经呼吸反应。将这些反应与镇静性安定药地西泮的作用进行了比较。丁螺环酮对呼吸输出具有剂量依赖性刺激作用,主要是通过增加潮气量,但在一些动物中也伴有频率增加。与此相关的是,无呼吸阈值向较低的PCO2水平偏移,而二氧化碳反应曲线的斜率或形状没有改变。相比之下,地西泮导致呼吸抑制,无呼吸阈值向较高的PCO2水平偏移。这些发现表明,丁螺环酮没有地西泮典型的神经呼吸抑制作用,而是刺激呼吸。尽管这些发现需要证明适用于人类,但它们表明丁螺环酮可能是一种治疗焦虑症患者的有用药物,而不会引起不良的呼吸抑制。