A pharmacokinetic analysis of the vagal release of 5-hydroxytryptamine in the cat.

The kinetics of 5-hydroxytryptamine (5-HT) release into the portal system after efferent electrical vagal stimulation were studied in an in vivo model. Blood samples were drawn from cats before, during and after vagal nerve stimulation, and portal plasma levels of 5-HT were measured. Portal plasma concentration of 5-HT rose during stimulation. After termination of stimulation, the plasma levels returned to steady state values and were used to calculate half-life and elimination rate constant. When pharmacokinetic principles were applied, the plasma half-life (T1/2) was determined to be 1.32 min and the elimination rate constant (KE), 0.5246 min-1. Pharmacokinetic principles also were applied to data from earlier in vitro studies using exogenously administered 5-HT, and a half-life of 1.03 min and a KE of 0.67 min-1 were calculated. Therefore, it appears that exogenously administered 5-HT and neurogenically released endogenous 5-HT are metabolized at a similar rate, both having a short half-life.