Effect of SR 49059, a V1a vasopressin receptor antagonist, in Raynand's phenomenon

Objective. To assess whether vasopressin V1a receptor blockade reduces the abnormal vasoactive response to cold in patients suffering from Raynaud's p henomenon (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 st udy with two 7-day periods of treatment separated by 21 days of washout. Bi lateral finger systolic blood pressure and skin temperature were assessed b efore and after immersion of the hand in cold water for 3 min (15 degreesC) during the screening phase and three times (before and 2 and 4 h after dru g 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 af ter the end of the cold immersion test. Results. SR 49059 significantly attenuated the cold-induced fall in systoli c pressure by 14.5% (95% confidence interval 0-29. P = 0.045) on the most a ffected 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 4905 9 on day 7 (P = 0.060 and P = 0.062 respectively). The beneficial effects o n finger pressure and temperature recovery were obtained without changes in supine blood pressure or in heart rate. Conclusion. SR 49059 given orally once a day for 7 days to patients with RP showed favourable effects compared with placebo on finger systolic pressur e and temperature recovery after cold immersion, without inducing side-effe cts.