蝙蝠葛碱衍生物D_3对呼吸的影响及抗吗啡、甲苯噻嗪抑制呼吸的效果

Effect of Dauricine Derivative D_3 on Respiration and Its Antagonism of Respiratory Inhibition Induced by Morphine and Xylazine

蝙蝠葛碱衍生物D_3 3 mg/kg iv引起麻醉大鼠呼吸频率加快,PNAP、IcEMAP幅度增大;2 mg/kg iv也使麻醉猫呼吸加快,每分通气量增加,并能分别部分对抗吗啡和甲苯噻嗪所致的呼吸抑制。等剂量蝙蝠葛碱对麻醉大鼠的呼吸兴奋不明显,但降低吗啡抑制呼吸后的死亡率有同等效果。D_3的呼吸兴奋作用可能与丙酰基取代了蝙蝠葛碱羟基中的氢、提高了分子的疏水性和增强了对钙调素的抑制活性有关,其药理机制尚待进一步探讨。

The increase of respiratory frequency(RF) and the magnitude of increase in the action potentials of phrenic nerve (PNAP) and of musculi intercostales externi (IcEMAP) were produced by dauricine derivative D_3 iv 3 mg/kg in anesthetized rat. The increase of RF and the minute respiratory volume (MRV) were also found in anesthetized cat in which D_3 was administered intravenously at a dose of 2 mg/kg. Both doses of D_3 were able to partly antagonize the morphine-and xylazine-induced inhibition of respiration in these species. In the rat, Dau that was given intravenously in same dosage as D_3 did not have obvious stimulation of respiration, but it could also partly antagonize the effect of morphine in inhibiting respiration. It is suggested suggest that the respiratory stimulation produced by D_3 is probably related to that a propionyl is substituted for the hydrogen atom in the hydroxy of Dau, so that the molecular hydrophobicity and the activity of antagonizing CaM are elevated. However, further studies remain to be made to reveal its mechanism of pharmacologic action.