Effect of SR 49059, a V1a vasopressin receptor antagonist, in Raynaud's phenomenon.
OBJECTIVE
To assess whether vasopressin V1a receptor blockade reduces the abnormal vasoactive response to cold in patients suffering from Raynaud's phenomenon (RP).


METHODS
SR 49059, an orally active, non-peptidic vasopressin V1a receptor antagonist, was given orally (300 mg once daily) to 20 patients with RP in a single-centre, double-blind, placebo-controlled, randomized cross-over study with two 7-day periods of treatment separated by 21 days of washout. Bilateral finger systolic blood pressure and skin temperature were assessed before and after immersion of the hand in cold water for 3 min (15 degrees C) during the screening phase and three times (before and 2 and 4 h after drug intake) on days 1 and 7 of each of the two treatment periods. Recovery of digital pressure and skin temperature was measured 0, 10, 20 and 32 min after the end of the cold immersion test.


RESULTS
SR 49059 significantly attenuated the cold-induced fall in systolic pressure by 14.5% (95% confidence interval 0-29; P = 0.045) on the most affected hand on day 7 compared with placebo. Temperature recovery after the end of the cold test showed a trend to enhancement 2 and 4 h after SR 49059 on day 7 (P = 0.060 and P = 0.062 respectively). The beneficial effects on finger pressure and temperature recovery were obtained without changes in supine blood pressure or in heart rate.


CONCLUSIONS
SR 49059 given orally once a day for 7 days to patients with RP showed favourable effects compared with placebo on finger systolic pressure and temperature recovery after cold immersion, without inducing side-effects.
Hayoz
D
D
Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland.
Bizzini
G
G
Noël
B
B
Depairon
M
M
Burnier
M
M
Fauveau
C
C
Rouillon
A
A
Brouard
R
R
Brunner
H R
HR
D000328:Adult; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D001794:Blood Pressure / Q000187:drug effects; D003080:Cold Temperature; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005385:Fingers / Q000503:physiopathology; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D007101:Immersion; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000627:therapeutic use*; D011928:Raynaud Disease / Q000188:drug therapy* / Q000503:physiopathology; D012881:Skin Temperature / Q000187:drug effects
D065092:Antidiuretic Hormone Receptor Antagonists; D006727:Hormone Antagonists; D007211:Indoles; D011759:Pyrrolidines; C082134:relcovaptan