Tachyphylaxis to d-amphetamine: a reexamination of the phenomenon

Single or multiple injections of d-amphetamine (10(-3)--10(0) mg/kg) were administered to rats, after which steady-state blood levels of drug were determined. After single injections of d-amphetamine, there was a linear relationship between amount of administered drug and steady-state blood level of drug. After multiple injections of d-amphetamine, steady-state blood levels of drug conformed to the equation D = Doe--kappaepsilont. An attempt was made to relate steady-state blood levels of drug to steady-state responses (e.g., increase in blood pressure or heart rate). At steady-state, amphetamine-induced pressor responses were too small to be analyzed, but tachycardic responses were easily analyzed. It was found that steady-state heart rate responses were dose related to steady-state blood levels of drug. This was true regardless of whether d-amphetamine was administered once or repeatedly. The data indicate that, when tested in rats at sub-toxic doses, d-amphetamine does not evoke tachyphylaxis in relation to heart rate responses which are measured under steady-state conditions.