Effect of long-term ketanserin treatment on 5-HT levels, platelet aggregation and peripheral circulation in patients with Raynaud's phenomenon. A double-blind, placebo-controlled cross-over study

Abstract

The long-term effects of the serotonergic (5-hydroxy-tryptamine, 5-HT) receptor antagonist, ketanserin, on 5-HT levels in whole blood, platelet aggregation and peripheral circulation were investigated in a double-blind placebo-controlled cross-over study. In 13 patients with Raynaud's phenomenon, 5-HT and catecholamine levels in whole blood were determined and platelet aggregation assayed after addition of ADP, collagen and 5-HT. Peripheral circulation was evaluated with fingertip temperatures and finger plethysmography before and after local cooling, with measurements repeated after indirect sympathetic blockade by body warming and after alcohol. Patients' symptoms were continuously registered in an individual diary. All measurements were performed 8 to 12 hours after the last drug intake. Five of seven scleroderma patients reported beneficial effects of ketanserin treatment and all six patients with primary Raynaud's phenomenon reported less severe and shorter cold-induced attacks. 5-HT levels in whole blood were significantly reduced after 5 weeks of ketanserin treatment (p less than 0.001) with a tendency for persistence of this reduction after halting of the medication (a "carry-over" effect). Platelet aggregation velocity induced by ADP, collagen and 5-HT was unaffected after ketanserin treatment. The diastolic blood pressure in these patients was decreased from 77.5 mmHg to 71.0 mmHg (p less than 0.001) after ketanserin, but the finger systolic blood pressure (FSBP) was unchanged. After sympathetic blockade by body warming, patients with ketanserin treatment had a paradoxical reduction in both FSBP and finger-tip temperatures, which makes a supposed alpha-receptor-blocking effect of ketanserin less likely. The reduced 5-HT levels in whole blood may explain the subjective favourable effect on patients with Raynaud's phenomenon.