Neurokinin-1 receptor antagonist R116301 inhibits substance P-induced venodilation.
OBJECTIVE
To test the effect of the neurokinin-1 receptor antagonist hydroxybutanedioate (R116301) in human hand veins in vivo.


METHODS
In a randomized, double-blind, placebo-controlled crossover study we used the hand vein compliance method to evaluate the inhibition of the response to substance P by R116301.


RESULTS
In hand veins preconstricted with phenylephrine to 21% +/- 2.6% (mean +/- SEM, placebo) and 25% +/- 3.0% (R116301) of the initial diameter, substance P resulted in a mean venodilation of 84% +/- 7% and 87% +/- 13% (P = .8) before administration of placebo and R116301, respectively. Oral administration of 300 mg R116301 resulted in peak plasma concentrations of 1.16 +/- 0.1 microg/mL within 128 +/- 14 minutes. With increasing R116301 plasma concentrations, substance P-induced venodilation decreased significantly (P < .001), whereas placebo had no effect. Mean substance P-induced venodilation was markedly reduced to 8% +/- 7%.


CONCLUSIONS
This study confirms the presence of neurokinin-1 receptors in human veins and the effectiveness of the neurokinin-1 receptor antagonist R116301 in human hand veins.
Romerio
S C
SC
Department of Internal Medicine, University Hospital, Basel, Switzerland.
Linder
L
L
Haefeli
W E
WE
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D000440:Butanols / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006225:Hand / Q000098:blood supply; D006801:Humans; D008293:Malates; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D012016:Reference Values; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects
D000440:Butanols; D008293:Malates; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; C400708:R116301; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013373:Substance P