Successful Treatment of Raynaud's Syndrome with Prostacyclin

Belch, J J F; Newman, Peter; Drury, John; Capell, Hilary A.; Leiberman, P; James, W. B.; Forbes, C.D.; Prentice, C. R. M.

doi:10.1055/s-0038-1650182

Cited by 55 publications

(22 citation statements)

References 4 publications

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“…One explanation of this could be that the prostaglandin endoperoxides normally required to form TXA2 are diverted initially to the formation of vasoconstrictor prostaglandins rather than the vasodilator prostaglandin, PGI2. PGI2 has been shown to increase hand temperatures when given in therapeutic doses (Belch et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

Dazoxiben, a thromboxane synthetase inhibitor, in the treatment of Raynaud's syndrome: a double‐blind trial.

Belch¹,

Cormie²,

Newman³

et al. 1983

Brit J Clinical Pharma

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1 UK-37248 (dazoxiben), an orally active thromboxane synthetase inhibitor, was evaluated in a double-blind trial of patients with severe Raynaud's syndrome. 2 Twenty patients were enrolled in the study. Eleven of these patients received dazoxiben 400 mg day and nine received matching placebo capsules. Treatment was given for 6 weeks and the patients reviewed at 2 weekly intervals during the study. 3 Assessment of response was judged by clinical symptoms and hand temperature measurements. Haematological and haemostatic studies were also carried out. 4 Results show a significant clinical improvement in patients receiving dazoxiben for six weeks Hand temperature measurements, and haematological and haemostatic blood tests remained unchanged, however, apart from the expected lowering in plasma thromboxane B2 levels. 5 The mechanism of action of the drug would appear not to be mediated through increased prostacyclin production and further studies are under way to determine how improvement has been obtained in these patients.

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Section: Discussionmentioning

confidence: 99%

Dazoxiben, a thromboxane synthetase inhibitor, in the treatment of Raynaud's syndrome: a double‐blind trial.

Belch¹,

Cormie²,

Newman³

et al. 1983

Brit J Clinical Pharma

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“…In fact, PGI2 and its analogue had beneficial effects on various experimental thrombosis and occlusive dis eases (14,38,39). Moreover, PGI2 has clinically been used to prevent the thrombus formation in the extracor poreal circulation (40,41) and the arterial diseases such as Burger (42) and Raynaud's disease (43,44).…”

Section: Effects On Extracorporeal Circulationmentioning

confidence: 99%

Antithrombotic Effects of KW-3635, a Thromboxane A2-Receptor Antagonist, in Guinea Pigs.

et al. 1994

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ABSTRACT-Antithrombotic effects of KW-3635, a newly synthesized thromboxane (TX) A2-receptor an tagonist, were studied in guinea pigs. In the extracorporeal circulation thrombosis model, the shunt was fill ed with thrombi, and reduction of platelet count and increase in plasma TXA2 concentration were observed. KW-3635 (30 and 100 mg/kg, p.o.) inhibited the thrombus formation in the shunt and prevented the decrease in platelet count in the circulating blood without affecting the red blood cell count. BM13,505 (30, 100 mg/kg, p.o.), another TXA2-receptor antagonist, and ticlopidine (300 mg/kg, p.o.), an antiplatelet drug, also inhibited the thrombus formation, while aspirin (10, 300 mg/kg, p.o.) did not. Peripheral arterial occlusive disease was induced by injection of sodium laurate into the femoral artery in guinea pigs. Daily oral administration of KW-3635 (3 30 mg/kg) significantly prevented the progression of vascular lesions. BM13,505 (3-30 mg/kg, p.o.) and ticlopidine (100 mg/kg, p.o.) also ameliorated the vascular lesions, whereas aspirin (10, 100 mg/kg, p.o.) did not. KW-3635 at concentrations up to 10-4 M did not affect coagulation parameters in vitro. These results suggest that TXA2 is involved in the pathogenesis of arterial thrombotic and ischemic disorders. KW-3635 may be useful for the treatment of thrombotic disease and peripheral arterial occlusive diseases.

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“…Pain relief was a striking feature, presumably associated with the increased blood flow as indicated by increased temperature of the hands and fingers (142). Belch and co-workers (143) have also reported successful treatment in 4 out of 5 patients and a double-blind clinical trial (144) has now confirmed these results in Raynaud's phenomenon. There was an overall improvement still present at 6 weeks in 6 of 7 patients receiving prostacyclin, but only in 1 of 7 receiving placebo.…”

Section: (D) Prostacyclin and Atherosclerosismentioning

confidence: 90%

Adventures and excursions in bioassay: the stepping stones to prostacyclin

Vane

1983

British J Pharmacology

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Physiology has spawned many biological sciences, amongst them my own field of pharmacology. No man has made a more important contribution to the fields of physiology and pharmacology than Sir Henry Dale (1875( -1968 (4)), biological techniques and bioassay have contributed very substantially to the development of the field. Bioassay has provided crucial information on the role of the lungs in the removal of circulating prostaglandins (5), the participation of prostaglandins in inflammatory reactions (6, 7), the contribution of prostaglandins to the autoregulation and maintenance of blood flow to the kidney (8-10), the inhibitory effect of aspirin-like drugs on the biosynthesis of prostaglandins (11-13), the mediation of pyrogen fever by prostaglandins (14), and the release of rabbit aorta-contracting substance (RCS; now identified as thromboxane A2, TXA2) from lungs during anaphylaxis (15, 16). Moreover in 1976, bioassay made possible the discovery of PGX, now renamed prostacyclin (PGI2), the latest member of the prostaglandin family (17)(18)(19)(20). Indeed, it is doubtful whether the biological significance of any of the unstable products of arachidonic acid metabolism would have been recognized without bioassay techniques. With extraordinary simplicity and convenience, by its very nature, bioassay distinguishes between the important biologically active compounds and their closely related but biologically unimportant metabolites.In this review I shall discuss the development of the cascade superfusion bioassay technique and some of the discoveries and concepts which arose from its application, leading up to the discovery and development of prostacyclin. The effects of prostacyclin in man and its clinical assessment (another application of bioassay) will also be discussed.Cascade superfusion bioassay (a) Development Most uses of bioassay involving smooth muscle demand high sensitivity and specificity. These aspects have been achieved first, by limiting the volume of fluid bathing the isolated tissue and second, by using an assay organ sensitive to, and relatively specific for, the test substances under study. Further specificity can be achieved by using a combination of several tissues which present a characteristic pattern of response to the test substance or substances. This takes advantage of the principle of parallel pharmacological assay, regarded by Gaddum (21) as strong evidence for the identity of a compound.Magnus (22) introduced the idea of suspending an isolated portion of smooth muscle in a chamber

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Successful Treatment of Raynaud's Syndrome with Prostacyclin

Cited by 55 publications

References 4 publications

Dazoxiben, a thromboxane synthetase inhibitor, in the treatment of Raynaud's syndrome: a double‐blind trial.

Dazoxiben, a thromboxane synthetase inhibitor, in the treatment of Raynaud's syndrome: a double‐blind trial.

Antithrombotic Effects of KW-3635, a Thromboxane A2-Receptor Antagonist, in Guinea Pigs.

Adventures and excursions in bioassay: the stepping stones to prostacyclin

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