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.