Concentrations of phenethylamine in dog following single doses and during intravenous self-administration

A gas chromatographic procedure is described which was used to measure concentrations of beta-phenethylamine (PEA) in dog plasma following single or multiple infusions. Plasma levels were determined immediately following drug infusions during PEA self-administration sessions. At a unit dose of 3 mg/kg/infusion the concentration of PEA ranged from 1 to 3.95 microgram/ml of plasma, and from 2.5 to 4.75 microgram/ml at a unit dose of 6 mg/kg/infusion. At the time of responding for another infusion the plasma concentration varied between 0.16 and 0.52 microgram/ml and between 0.08 and 0.26 microgram/ml, for the two doses, respectively. Whole-body concentrations of PEA during self-administration were estimated according to a one compartment, open model using experimentally determined plasma half-lives obtained from single dose studies and inter-infusion intervals. Relatively little accumulation of PEA was predicted according to this model which correlated well with the experimental data. During the course of a self-administration session plasma levels rose initially following the infusion and declined to relatively constant levels ("response concentrations") when a subsequent drug-seeking response was made. Significant differences in "response concentrations" were observed between dogs and between doses. It is suggested that this response pattern is related to the distribution and clearance rate of the drug from plasma and well-perfused tissues.