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The interaction of Ro15-4513 (5 mg/kg) with ethanol (3 g/kg, 60%w/v bolus) in dogs was investigated. Ro15-4513 challenge 120 minutes after a single ethanol dose had no significant effect on blood ethanol concentration or heart rate. In the same experiment, (1) blood acetaldehyde concentration was elevated to more than double the control value (vehicle only, no Ro15-4513), and (2) systolic blood pressure decreased to less than 60% of control. Further investigation revealed: (1) after Ro15-4513, area under the blood acetaldehyde vs time curve was more than twofold greater (p = 0.0006) than control, and the area under the systolic blood pressure vs time curve was 76% (p = 0.0027) of control. Based on these results, we propose that an inter-relationship exists between Ro15-4513, blood acetaldehyde concentration, and systolic blood pressure in ethanol intoxicated dogs.

Pharmacodynamic Response to Ro15-4513 in Ethanol Intoxicated Dogs