Azuma H, Miyazawa T
Nihon Yakurigaku Zasshi. 1975 Nov;71(8):823-31.
It has been reported that doxapram exhibits a remarkable stimulating effect on respiration in humans and various experimental animals. The present experiment was an attempt to investigate whether or not doxapram inhibits an atrial arrest induced by transmural stimulation and exogenously applied nicotine. Doxapram and dimorpholamine used as comparative agents showed transient and slightly positive responses followed by a negative one in the atrium preparation. Transmural stimulation under a condition of 30 V intensity with 0.3 msec duration at a frequency of 10 Hz for 2 sec caused an atrial arrest for about 3 sec followed by negative chronotropic and inotropic responses, and a positive one. All responses caused by transmural stimulation were hardly affected by pretreatment with doxapram at a concentration of 10(-5) g/ml or less, while dimorpholamine at a high concentration (10(-5)g/ml) showed an inhibition of atrial arrest and following negative responses. Negative chronotropic and inotropic responses caused by an application of nicotine were significantly inhibited by pretreatment with doxapram or dimorpholamine. Both doxapram and dimorpholamine at higher concentrations also inhibited the positive responses of the atrium caused by nicotine. Neither doxapram nor dimorpholamine affected the ACh-induced responses. NA-induced responses were uneffected by pretreatment with doxapram, while the responses were slightly potentiated by dimorpholamine. The action mechanisms of doxapram and dimorpholamine are discussed.
据报道，多沙普仑对人类和各种实验动物的呼吸具有显著的刺激作用。本实验旨在研究多沙普仑是否能抑制经壁刺激和外源性应用尼古丁诱导的心房停搏。用作对照剂的多沙普仑和双吗啉胺在心房标本中显示出短暂且轻微的阳性反应，随后为阴性反应。在强度为30V、持续时间为0.3毫秒、频率为10Hz的条件下进行2秒的经壁刺激，可导致心房停搏约3秒，随后出现负性变时性和变力性反应以及一个阳性反应。经壁刺激引起的所有反应在浓度为10(-5)g/ml或更低的多沙普仑预处理下几乎不受影响，而高浓度（10(-5)g/ml）的双吗啉胺则显示出对心房停搏及随后负性反应的抑制作用。应用尼古丁引起的负性变时性和变力性反应经多沙普仑或双吗啉胺预处理后受到显著抑制。较高浓度的多沙普仑和双吗啉胺也均抑制了尼古丁引起的心房阳性反应。多沙普仑和双吗啉胺均未影响乙酰胆碱诱导的反应。去甲肾上腺素诱导的反应在多沙普仑预处理下未受影响，而双吗啉胺则使这些反应略有增强。本文讨论了多沙普仑和双吗啉胺的作用机制。
