Nakamura T, Miura Y, Aihara K, Satoh H, Goto K, Tsumagari T
Nihon Yakurigaku Zasshi. 1983 Jul;82(1):79-92.
The effects of traxanox, an anti-allergic drug, on the cardiovascular system were studied in both anesthetized dogs and cats and in isolated heart preparations from guinea-pigs. In anesthetized dogs, a very small dose of traxanox (0.01 mg/kg, i.v.) had no effect, but 0.1--30 mg/kg caused an increase in respiratory rate, hypotension, bradycardia, a transient decrease followed by an increase in renal blood flow, and a decrease in femoral blood flow. These effects were abolished by vagal block, indicating they are mediated via vagal afferents. In contrast, oral administration of traxanox (100 mg/kg) had no effect on the blood pressure or heart rate of anesthetized dogs. In anesthetized cats, traxanox (3 and 30 mg/kg, i.v.) caused a slight increase in blood pressure, but showed no effect on respiratory rate and heart rate. Both traxanox and theophylline (10(-4)M) caused increases in the beat rate of the atria and the contractile force of the papillary muscle in isolated preparations from guinea-pigs, and they potentiated the positive chronotropic and inotropic responses induced by isoproterenol. On the other hand, in anesthetized and vagotomized dogs, traxanox (3 and 10 mg/kg, i.v.) affected neither the left ventricular contractile force nor the hypotension and positive inotropic and chronotropic responses produced by isoproterenol. Administration of theophylline alone (3 and 10 mg/kg, i.v.) caused hypotension and increases in contractile force and heart rate, but it did not enhance the responses produced by isoproterenol. At doses of 1 and 10 mg/kg (i.v.), traxanox had little effect on either pressor or chronotropic responses to norepinephrine, epinephrine, DMPP and stellate cardiac nerve stimulation. The same doses of traxanox slightly reduced the depressor and chronotropic responses to isoproterenol, acetylcholine and vagus nerve stimulation. These findings suggest that traxanox had no effect on the cardiovascular systems of the animals studied in the dose range (1--5 mg/kg, p.o.) showing anti-allergic activity.
研究了抗组胺药曲尼司特对麻醉犬、猫及豚鼠离体心脏标本心血管系统的影响。在麻醉犬中，极少量的曲尼司特（0.01mg/kg，静脉注射）无作用，但0.1 - 30mg/kg可引起呼吸频率增加、低血压、心动过缓、肾血流量先短暂减少后增加以及股血流量减少。迷走神经阻滞可消除这些作用，表明它们是通过迷走神经传入介导的。相比之下，口服曲尼司特（100mg/kg）对麻醉犬的血压或心率无影响。在麻醉猫中，曲尼司特（3和30mg/kg，静脉注射）可使血压略有升高，但对呼吸频率和心率无影响。曲尼司特和茶碱（10⁻⁴M）均可使豚鼠离体标本中的心房搏动率和乳头肌收缩力增加，且它们增强了异丙肾上腺素诱导的正性变时性和变力性反应。另一方面，在麻醉和迷走神经切断的犬中，曲尼司特（3和10mg/kg，静脉注射）对左心室收缩力以及异丙肾上腺素产生的低血压、正性变力性和变时性反应均无影响。单独给予茶碱（3和10mg/kg，静脉注射）可引起低血压以及收缩力和心率增加，但未增强异丙肾上腺素产生的反应。静脉注射1和10mg/kg剂量的曲尼司特对去甲肾上腺素、肾上腺素、二甲基苯基哌嗪（DMPP）和星状心神经刺激引起的升压或变时性反应几乎无影响。相同剂量的曲尼司特可略微降低对异丙肾上腺素、乙酰胆碱和迷走神经刺激的降压和变时性反应。这些发现表明，在显示抗过敏活性的剂量范围（1 - 5mg/kg，口服）内，曲尼司特对所研究动物的心血管系统无影响。
