Szeto H H, Zhu Y S, Umans J G, Dwyer G, Clare S, Amione J
Department of Pharmacology, Cornell University Medical College, New York, New York.
J Pharmacol Exp Ther. 1988 May;245(2):537-42.
Morphine has been reported to both stimulate and suppress fetal breathing movements (FBM). In light of these conflicting reports, we have conducted a systematic dose-response analysis of the effects of morphine on FBM in 27 fetal lambs. Morphine was infused directly to the fetus in doses ranging from 0.075 to 80 mg/hr. Low doses (0.075-2.5 mg/hr) resulted in a progressive increase in the relative incidence of FBM, whereas higher doses (greater than 2.5 mg/hr) decreased FBM with total apnea observed at 80 mg/hr. This biphasic response can be fitted as the sum of two sigmoidal log dose-response curves. Both stimulation and suppression of FBM by morphine were abolished by naloxone pretreatment, indicating that both responses are mediated by activation of opioid receptors. The dual action of morphine on FBM may be due to different opioid receptor subtypes or different sites of action.
据报道，吗啡既能刺激又能抑制胎儿呼吸运动（FBM）。鉴于这些相互矛盾的报道，我们对27只胎羊进行了吗啡对FBM影响的系统剂量反应分析。吗啡以0.075至80毫克/小时的剂量直接注入胎儿体内。低剂量（0.075 - 2.5毫克/小时）导致FBM相对发生率逐渐增加，而高剂量（大于2.5毫克/小时）则降低FBM，在80毫克/小时时观察到完全呼吸暂停。这种双相反应可以拟合为两条S形对数剂量反应曲线的总和。纳洛酮预处理消除了吗啡对FBM的刺激和抑制作用，表明这两种反应均由阿片受体激活介导。吗啡对FBM的双重作用可能是由于不同的阿片受体亚型或不同的作用部位。
