Weinstock M, Erez E, Roll D
J Pharmacol Exp Ther. 1981 Aug;218(2):504-8.
The influence of physostigmine was studied on the effect of morphine on the cardiovascular and respiratory systems in conscious rabbits. Morphine (4 mg/kg i.v.) caused analgesia, bradycardia, hypotension and respiratory depression, as indicated by a fall in respiratory rate of 50%, a rise in blood PaCO2 from 25.1 to 37.2 mm Hg and a fall in pH from 7.40 to 7.24. These effects lasted 2 to 3 hr and were completely antagonized by naloxone. Physostigmine (2.5 or 5 microgram/kg/min) given by constant i.v. infusion did not significantly alter blood pressure or heart rate, but decreased blood PaCO2 from 25.1 to 19 mm Hg and increased pH from 7.40 to 7.46. Pretreatment of rabbits with physostigmine (5 microgram/kg/min) completely prevented both the fall in blood pressure and blood pH and the rise in PaCO2 induced by morphine (4 mg/kg) and also significantly reduced both the intensity and duration of bradycardia. Analgesics activity of morphine remained unimpaired by physostigmine. Neostigmine (2.5 microgram/kg/min) potentiated the bradycardia induced by morphine and did not antagonize its hypotensive and respiratory depressant effects. The results support the hypothesis that the respiratory and cardiovascular depressant effects of morphine, but not the analgesia, results from an inhibition of acetylcholine release from neurons in the central nervous system.
研究了毒扁豆碱对清醒家兔体内吗啡作用于心血管和呼吸系统的影响。静脉注射吗啡（4毫克/千克）可引起镇痛、心动过缓、低血压和呼吸抑制，表现为呼吸频率下降50%，血液中二氧化碳分压从25.1毫米汞柱升至37.2毫米汞柱，pH值从7.40降至7.24。这些作用持续2至3小时，并被纳洛酮完全拮抗。持续静脉输注毒扁豆碱（2.5或5微克/千克/分钟）对血压和心率无显著影响，但可使血液中二氧化碳分压从25.1毫米汞柱降至19毫米汞柱，pH值从7.40升至7.46。家兔预先用毒扁豆碱（5微克/千克/分钟）处理，可完全防止吗啡（4毫克/千克）引起的血压下降、血液pH值下降和二氧化碳分压升高，还可显著减轻心动过缓的强度和持续时间。毒扁豆碱不影响吗啡的镇痛活性。新斯的明（2.5微克/千克/分钟）增强了吗啡引起的心动过缓，且不拮抗其降压和呼吸抑制作用。这些结果支持以下假说：吗啡的呼吸和心血管抑制作用而非镇痛作用，是由于中枢神经系统神经元乙酰胆碱释放受抑制所致。
