Effect of dazoxiben, a thromboxane synthetase inhibitor on skin-blood flow following cold challenge in patients with Raynaud's phenomenon.
The effects of dazoxiben on finger-blood flow in response to cold challenge were studied in normal subjects and patients with Raynaud's phenomenon. In normal subjects concentrations of TXB2 and 6-oxo-PGF1 alpha were measured in blood taken from dorsal hand veins following cold challenge. In a parallel multicentre study we examined the effects of dazoxiben on finger temperature and capillary blood cell velocity in patients with Raynaud's phenomenon. Dazoxiben did not affect finger arterial inflow at rest or during cold challenge in patients or controls. However in both groups, recovery was quicker after cold challenge on dazoxiben treatment. In patients median flow was 5 ml (100(-1) ml) min-1 (range 1-10) v. 2 (0.5-15), P less than 0.05 dazoxiben v. placebo at 15 min after cold challenge. However, in normal subjects this did not prove to be statistically significant. In normal subjects there was a fall in TXB2 concentrations and relative rise in 6-oxo-PGF1 alpha following dazoxiben treatment indicating redirection of prostaglandin endoperoxides towards synthesis of PGI2. Comparison of the sum-total output of each eicosanoid following treatment with dazoxiben revealed a 65% reduction in TXB2 concentrations (P less than 0.025 compared with placebo) and a 40% increase in 6-oxo-PGF1 alpha concentrations (P less than 0.05 compared with placebo). However a simultaneous increase in concentrations of FPA indicated generation of thrombin, probably at the needle tip. Long-term treatment with dazoxiben resulted in no significant change in finger-skin temperature or capillary blood cell velocity, duration, or severity of attacks of Raynaud's phenomenon.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D003080:Cold Temperature; D004341:Drug Evaluation; D005260:Female; D005344:Fibrinopeptide A / Q000032:analysis; D005385:Fingers / Q000098:blood supply; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011897:Random Allocation; D011928:Raynaud Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D013928:Thromboxane A2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D007093:Imidazoles; C029166:dazoxiben; D005344:Fibrinopeptide A; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase