Effect Of Guanethidine Cocaine And Reserpine On Hypotensive Action Of Thiopental

The effects of reserpine, guanethidine and cocaine on the amount of thiopental required for a 50-mm decrease in mean arterial blood pressure have been investigated. The dose of thiopental required for the hypotensive response was less in animals pretreated with reserpine (0.1 mg/kg/day for 2 days) than in control dogs. In contrast, guanethidine (10 mg/kg/day for 2 days) did not alter the dose of thiopental necessary for the hypotensive effect and cocaine (5 mg/kg, administered acutely) actually increased the dose required. It was found that the animals receiving guanethidine or cocaine were supersensitive to exogenous norepinephrine but those receiving this particular schedule of pretreatment with reserpine were not. Previous work has suggested that the increased sensitivity to hypotension induced by thiopental as seen in animals receiving reserpine is due to marked depletion of norepinephrine from the myocardium. It is suggested that the susceptibility to hypotension produced by thiopental in the dogs receiving guanethidine is unchanged in spite of depletion of norepinephrine because the small amounts of still releasable norepinephrine are potentiated by the cocaine-like effect of guanethidine.