D.: Antagonism of the cardiovascular and respiratory depressant effect of morphine in the conscious rabbit by physostig- nd reprint requests to: Dr. Marts Weinstock, Department of Pharmacology mine

cardiovascular and respiratory depressant effects of morphine in the conscious rabbit by physostigmine. J. Pharmacol. Exp. Ther. 218: 504-508, 1981. The influence of physostigmine was studied on the effect of morphine on the cardiovascular and respiratory systems in conscious rabbits. Morphine (4 mg/kg iv.) caused analgesia, bradycardia, hypotension and respiratory depression, as mdi-cated by a fall in respiratory rate of 50%, a rise in blood Pac0, 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 g/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 1 9 mm Hg and increased pH from 7.40 to 7.46. Pretreatment of rabbits with physostigmine (5 tg/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. Analgesic activ-ity of morphine remained unimpaired by physostigmine. Neo-stigmine (2.5 ig/kg/min) potentiated the bradycardia induced by morphine and did not antagonize its hypotensive and res-piratory depressant effects. The results support the hypothesis that the respiratory and cardiovascular depressant effects of morphine, but not the analgesia, result from an inhibition of acetylcholine release from neurons in the central nervous sys-tem. Injection of acetylcholine and other muscarinic agonists into the lateral ventricle or cisterna magna of dogs and rats results in a rise in blood pressure and tachycardia (Lang and Rush