Ketanserin for Raynaud's phenomenon in progressive systemic sclerosis

Pope, Janet; Fenlon, Deborah; Thompson, Alexandra; Shea, Beverley; Furst, D E; Wells, George A.; Silman, Alan J.

doi:10.1002/14651858.cd000954

Cited by 30 publications

(24 citation statements)

References 27 publications

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“…Side effects were 6 times more common when treated with ketanserin. The frequency of attacks did not change, but the duration of attacks decreased signifi cantly in the ketanserin group [ 69 ]. Ketanserin is not recommended or available, but blocking 5HT receptor may have benefi ts and new agents should be studied.…”

Section: -Hydroxytryptamine (5ht) Receptor Antagonist Ketanserinmentioning

confidence: 97%

Drug Treatment of Raynaud’s Phenomenon

Pope

2014

Raynaud’s Phenomenon

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Section: -Hydroxytryptamine (5ht) Receptor Antagonist Ketanserinmentioning

confidence: 97%

Drug Treatment of Raynaud’s Phenomenon

Pope

2014

Raynaud’s Phenomenon

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“…Ketanserin, ein weiterer Serotoninantagonist, zeigte in einer Cochrane-Analyse allerdings keinen Effekt auf die Behandlung des RP [40].…”

Section: Selektive Serotonin-wiederaufnahmehemmerunclassified

Raynaud-Phänomen in der Dermatologie

Sunderkötter

Riemekasten²

2006

Hautarzt

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While primary Raynaud phenomenon (RP) only rarely leads to complications, secondary RP when associated with systemic sclerosis (SSc) frequently results in necrosis, ulcers or even gangrene. Therefore timely therapeutic intervention is required. Management of RP includes physical therapy, avoidance of triggers, and a variety of medications, depending on the disease severity. On the basis of published studies and of our own experience we suggest: a) for primary and uncomplicated secondary RP, calcium channel blockers in adequate doses; b) for SSc-associated secondary RP with hypertension, cardial or renal involvement, drugs which interfere with angiotensin; c) in case of concomitant depression, exploitation of the vasodilatory effects of serotonin reuptake inhibitors, d) in presence of ulcers or marked trophic alterations, intravenous administration of iloprost, e) for recalcitrant cases and endangered digits, sildenafil, f) for prevention of severe relapses, the endothelin-receptor antagonist bosentan. The drugs mentioned in c-f are not approved for RP and used off-label. In patients with secondary SSc-associated RP, timely therapy can reduce the percentage of complications such as ulcers or amputations. In addition, timely treatment of RP possibly retards ensuing fibrotic processes.

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“…Several mechanisms have been proposed to mediate the exaggerated vasoconstriction in Raynaud's phenomenon, such as enhanced endothelin levels, augmented serotonin release, or increased activation of the renin-angiotensin system; however, experimental findings do not support the involvement of these factors (Pope et al, 2000;Wood and Ernst, 2006;Nguyen et al, 2010). In contrast, the role of a 2 -adrenergic receptors (a 2 -ARs) in cold-induced vasoconstriction was demonstrated in the mid1990s by results showing that vasospastic attacks in Raynaud's phenomenon patients were prevented by the a 2 -AR antagonist yohimbine, but not by the a 1 -AR blocker prazosin (Freedman et al, 1995).…”

Section: Introductionmentioning

confidence: 98%

Molecular Determinants of the Human α_2C-Adrenergic Receptor Temperature-Sensitive Intracellular Traffic

2015

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The human a 2C -adrenergic receptor (a 2C -AR) is localized intracellularly at physiologic temperature. Decreasing the environmental temperature strongly stimulates the receptor transport to the cell surface. In contrast, rat and mouse a 2C -AR plasma membrane levels are less sensitive to decrease in temperature, whereas the opossum a 2C -AR cell surface levels are not changed in these conditions. Structural analysis demonstrated that human a 2C -AR has a high number of arginine residues in the third intracellular loop and in the C-terminus, organized as putative RXR motifs. Although these motifs do not affect the receptor subcellular localization at 37°C, deletion of the arginine clusters significantly enhanced receptor plasma membrane levels at reduced temperature. We found that this exaggerated transport of the human receptor is mediated by two functional arginine clusters, one in the third intracellular loop and one in the C-terminus. This effect is mediated by interactions with COPI vesicles, but not by 14-3-3 proteins. In rat a 2C -AR, the arginine cluster from the third intracellular loop is shifted to the left due to three missing residues. Reinsertion of these residues in the rat a 2C -AR restored the same temperature sensitivity as in the human receptor. Proteomic and coimmunoprecipitation experiments identified pontin as a molecule having stronger interactions with human a 2C -AR compared with rat a 2C -AR. Inhibition of pontin activity enhanced human receptor plasma membrane levels and signaling at 37°C. Our results demonstrate that human a 2C -AR has a unique temperature-sensitive traffic pattern within the G protein-coupled receptor class due to interactions with different molecular chaperones, mediated in part by strict spatial localization of specific arginine residues.

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Ketanserin for Raynaud's phenomenon in progressive systemic sclerosis

Abstract: Engelhart 1988 {published data only} Engelhart M. Ketanserin in the treatment of Raynaud's phenomenon associated with generalized scleroderma. British

Cited by 30 publications

References 27 publications

Drug Treatment of Raynaud’s Phenomenon

Drug Treatment of Raynaud’s Phenomenon

Raynaud-Phänomen in der Dermatologie

Molecular Determinants of the Human α_2C-Adrenergic Receptor Temperature-Sensitive Intracellular Traffic

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Ketanserin for Raynaud's phenomenon in progressive systemic sclerosis

Abstract: Engelhart 1988 {published data only} Engelhart M. Ketanserin in the treatment of Raynaud's phenomenon associated with generalized scleroderma. British

Cited by 30 publications

References 27 publications

Drug Treatment of Raynaud’s Phenomenon

Drug Treatment of Raynaud’s Phenomenon

Raynaud-Phänomen in der Dermatologie

Molecular Determinants of the Human α2C-Adrenergic Receptor Temperature-Sensitive Intracellular Traffic

Contact Info

Product

Resources

About

Molecular Determinants of the Human α_2C-Adrenergic Receptor Temperature-Sensitive Intracellular Traffic