A COMPARISON OF THE EFFECTS OF 2 PUTATIVE 5-HYDROXYTRYPTAMINE RENAL PRODRUGS IN NORMAL MAN

1 The effects of 1 h intravenous infusions of equimolar amounts of two putative 5-hydroxytryptamine (5-HT) renal prodrugs, 5-hydroxy-L-tryptophan (5-HTP, 10 mug kg-1 min-1) and gamma-L-glutamyl-5-hydroxy-L-tryptophan (glu-5-HTP, 16.6 mug kg-1 min-1) were examined in five healthy male volunteers in a randomised, placebo-controlled, cross-over study. 2 Both compounds increased urinary excretion of 5-HT and there was greater extra-renal formation of 5-HT following 5-HTP administration than after glu-5-HTP. 3 Glu-5-HTP was significantly antinatriuretic. 5-HTP reduced mean urinary sodium excretion but this effect was not statistically significant. 4 5-HTP, but not glu-5-HTP, significantly increased plasma aldosterone. There was no increase in plasma renin activity with either compound. 5 There were no significant changes in pulse rate or blood pressure. Two subjects complained of nausea at the end of 5-HTP infusion but none had any adverse reactions with glu-5-HTP. 6 The results of this study suggest that both prodrugs generate 5-HT in man and that glu-5-HTP is antinatriuretic. The glutamyl derivative may have greater renal specificity than 5-HTP and, as a result, causes less systemic side effects.