TACHYPHYLAXIS TO D-AMPHETAMINE - RE-EXAMINATION OF PHENOMENON

  • 1 January 1978
    • journal article
    • research article
    • Vol. 206  (2) , 331-338
Abstract
Single or multiple injections of d-amphetamine (10-3-100 mg/kg) were administered to [male Wistar] 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 = .**GRAPHIC**. where D = blood level of drug at time t; D0 = initial blood level of drug; e the number used as the base of natural logarithims; and k.epsilon. is the rate constant for elimination. 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. 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. When tested in rats at sub-toxic doses, d-amphetamine apparently does not evoke tachyphylaxis in relation to heart rate responses measured under steady-state conditions.