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The effect of chlorpromazine (0.5 and 4 mg/kg) on plasma catecholamines (adrenaline and noradrenaline) concentrations was investigated in rats. After an i.v. bolus administration of chlorpromazine, plasma adrenaline and noradrenaline concentrations showed a dose dependent increase. In order to clarify the pharmacokinetics of catecholamines in plasma, i.v. infusion of adrenaline or noradrenaline was also carried out. Plasma catecholamines after i.v. infusion showed typical characteristics of a one compartment model with a zero order production rate of endogenous catecholamines. From the data observed, a mathematical model was constructed to elucidate the relationship between the pharmacokinetics (brain concentrations) and the pharmacologic effect (plasma catecholamines concentrations) of chlorpromazine in rats. The results indicated that the time courses of plasma adrenaline and noradrenaline concentrations after an i.v. administration of chlorpromazine were described reasonably well by a simple pharmacokinetic-pharmacodynamic model.

A kinetic study of chlorpromazine on the hyperglycemic response in rats. I. Effect of chlorpromazine on plasma catecholamines.