Physiologic effects and plasma kinetics of phenylethanolamine and its N-methyl homolog in the dog.

Single i.v. doses of the endogenous trace amine phenylethanolamine (PEOH) and its N-methyl homolog (NMPEOH) were administered to separate groups of five dogs. The dose- and time-related effects of these compounds were measured on pupillary diameter, heart rate and body temperature. Blood samples were obtained concurrently with the physiologic measures and plasma levels of PEOH and NMPEOH were determined by gas chromatography. Both compounds dilated pupils, decreased heart rate and tended to lower body temperature. NMPEOH was approximately 1.25 times more potent than PEOH in dilating pupils. The plasma pharmacokinetics of both PEOH and NMPEOH could be described by a biexponential function with half-lives for the elimination phase of approximately 30 to 60 min. Plasma levels correlated significantly with increases in pupil diameter for both drugs, but only plasma levels of NMPEOH correlated significantly with changes in heart rate or body temperature. The present findings demonstrate that the endogenous trace amine PEOH and its N-methyl homolog NMPEOH, which may be produced endogenously by the enzymatic action of phenylethanolamine-N-methyl-transferase, produce prominent physiologic effects when administered i.v. in the dog, thus suggesting they may have physiologic roles in mammalian nervous system function.