A comparison of the effects of two 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 micrograms kg-1 min-1) and gamma-L-glutamyl-5-hydroxy-L-tryptophan (glu-5-HTP, 16.6 micrograms 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.