Acute tolerance to subjective but not cardiovascular effects of d-amphetamine in normal, healthy men.
This is a descriptive report on the relationship between the pharmacokinetics and pharmacodynamics of d-amphetamine in healthy, normal volunteers. Six men, aged 22 to 31, attended two experimental sessions during which they received single oral doses of 20 mg of d-amphetamine. Plasma levels of drug and measures of drug effect were collected predrug and at regular intervals for 24 hours after drug administration. Plasma drug levels peaked at 4 hours and remained at detectable levels for 24 hours after drug administration. Subjective ratings, including "feel drug" and "feel high" peaked at 1 1/2 to 2 hours and returned to baseline levels by 3 to 4 hours. Evaluation of phase plots (i.e., drug effect vs. drug concentration) indicated that acute tolerance developed to the subjective but not to the cardiopressor effects of d-amphetamine. This finding implies that individuals who repeatedly administer the drug to maintain certain levels of subjective effects may increase plasma drug levels and physiologic effects to toxic levels.
Brauer
L H
LH
Department of Psychiatry, University of Chicago, IL 60637, USA.
Ambre
J
J
De Wit
H
H
D000328:Adult; D000339:Affect / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004361:Drug Tolerance; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male
D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine