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Pento barbital causes cardio respiratory depression by interacting with a gamma amino butyric acid ergic system at the ventral surface of the medulla



Pento barbital causes cardio respiratory depression by interacting with a gamma amino butyric acid ergic system at the ventral surface of the medulla



Journal of Pharmacology & Experimental Therapeutics 226(2): 349-355



A tonically active GABA system at Schlaefke's area (intermediate area) on the ventral surface of the medulla exerts control over cardiorespiratory function. This is the same site where Feldberg and Guertzenstein elicited pentobarbital-induced hypotension. To determine whether pentobarbital-induced cardiorespiratory depression is mediated by a GABAergic mechanism at this site, this agent was applied locally to the intermediate area in 8 chloralose-anesthetized cats while monitoring respiratory activity, blood pressure and heart rate. Pentobarbital (0.5-1.5 mg) reduced minute ventilation from 383 .+-. 19 to 227 .+-. 31 ml/min (P < 0.05) by reducing tidal volume from 29.8 .+-. 2.4 to 16.1 .+-. 1.6 ml (P < 0.05), without changing respiratory rate. Mean blood pressure and heart rate were reduced from 150 .+-. 16 mm Hg and 182 .+-. 8 beats/min to 73 .+-. 16 mm Hg and 136 UU 12 beats/min (P < 0.05), respectively. Respiratory depression culminated in apnea in each animal tested. Bicuculline applied to the intermediate area in doses that selectively counteract GABA-induced apnea (5.0-17.5 .mu.g) reestablished breathing, mean arterial pressure and heart rate to values equal to or greater than control levels. This dose range of bicuculline had no effect on heroin-induced respiratory depression. Cardiorespiratory depression observed with i.v. administration of pentobarbital in 4 cats was reversed by bicuculline (10-20 .mu.g) applied to the intermediate area. Pentobarbital evidently acts at the intermediate area to activate a GABAergic system resulting in cardiorespiratory depression.

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