吗啡的呼吸抑制作用与中枢胆碱能系统的关系

RELATIONSHIP BETWEEN MORPHINE-INDUCED RESPI-RATORY DEPRESSION AND THE CENTRAL CHOLINERGIC SYSTEM

本文以兔呼吸频率、通气量和血气作为指标,观察到iv吗啡0.5～4.0mg/kg产生剂量依赖性呼吸抑制。icv匹鲁卡品2.5mg/kg能完全逆转这一抑制效应。icv 4—氨基吡啶(4—AP),1.5μg/kg兴奋呼吸,并使吗啡量效曲线右移。用利血平耗竭儿茶酚胺后,吗啡仍能抑制呼吸,4—AP可消除之。表明吗啡抑制呼吸与中枢胆碱能系统有关,且可能系它抑制Ach释放所致。

Morphine(0.5, 1, 2 and 4 mg/kg, iv)caused dosage-dependent respiratory depression in conscious rabbits. The respiratory frequency and PaO2 were decreased, PaCO2 was increased. Although tidal volume was increased in all cases, significant reduction of ventilation volume was only observed after 2 and 4 mg/kg of morphine.4-Aminopyridine ( 4-AP, 1.5ug/kg, icv ) caused increase of respiratory rate and PaO2 and reduction of PaCO2, with marked increase in minute volume .When 4-AP was combined with different doses of morphine, the respiratory depressant effect was reduced and the dose-effect curve was shifted to the right. After reserpine ( 1.0 mg/kg, iv ) , morphine ( 4.0mg/kg, iv ) still decreased respiratory frequency by 54%and 4-AP (1.0ug/kg, icv ) cnuld abolish this effect completely. The respiratory depressant effect of morphine was reversed by pilocarpine ( 2.5 mg/kg, icv ) . The above results suggest that the depressant effect of morphine on respiration is related to central cholinergic system, maybe as a result of morphine's retarding the release of Ach.