Format

Send to

Choose Destination
Clin Pharmacol Ther. 1999 Nov;66(5):522-7.

Neurokinin-1 receptor antagonist R116301 inhibits substance P-induced venodilation.

Author information

1
Department of Internal Medicine, University Hospital, Basel, Switzerland.

Abstract

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%.

CONCLUSION:

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.

PMID:
10579480
DOI:
10.1016/S0009-9236(99)70016-0
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center