Phosphodiesterase Type 5 Inhibition Is a Novel Therapeutic Option in Raynaud Disease

Caglayan, Evren; Huntgeburth, Michael; Karasch, T; Weihrauch, Julia; Hunzelmann, Nicolas; Krieg, Thomas; Erdmann, Erland; Rosenkranz, Stephan

doi:10.1001/archinte.166.2.231

Cited by 81 publications

(52 citation statements)

References 20 publications

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“…E) OTHER POTENTIAL USES. Other possibilities for use of PDE5 inhibitors include treatment of Raynaud's disease (54,86,118), suppression of other autoimmune diseases (48, 343), and relief of symptoms associated with cystic fibrosis (67,222,223). Potential treatment of genitourinary tract dysfunctions (benign prostate syndrome, overactive bladder, and urge incontinence) has garnered a lot of attention (324,325,362,397,425), as has treatment of Peyronie's disease (128), premature ejaculation, and ureteral relaxation for passage of kidney stones (132,325).…”

Section: Expanded Uses For Approved Pde5 Inhibitorsmentioning

confidence: 99%

Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions

Francis

Blount

Corbin

2011

Physiological Reviews

567

546

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The superfamily of cyclic nucleotide (cN) phosphodiesterases (PDEs) is comprised of 11 families of enzymes. PDEs break down cAMP and/or cGMP and are major determinants of cellular cN levels and, consequently, the actions of cN-signaling pathways. PDEs exhibit a range of catalytic efficiencies for breakdown of cAMP and/or cGMP and are regulated by myriad processes including phosphorylation, cN binding to allosteric GAF domains, changes in expression levels, interaction with regulatory or anchoring proteins, and reversible translocation among subcellular compartments. Selective PDE inhibitors are currently in clinical use for treatment of erectile dysfunction, pulmonary hypertension, intermittent claudication, and chronic pulmonary obstructive disease; many new inhibitors are being developed for treatment of these and other maladies. Recently reported x-ray crystallographic structures have defined features that provide for specificity for cAMP or cGMP in PDE catalytic sites or their GAF domains, as well as mechanisms involved in catalysis, oligomerization, autoinhibition, and interactions with inhibitors. In addition, major advances have been made in understanding the physiological impact and the biochemical basis for selective localization and/or recruitment of specific PDE isoenzymes to particular subcellular compartments. The many recent advances in understanding PDE structures, functions, and physiological actions are discussed in this review.

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Section: Expanded Uses For Approved Pde5 Inhibitorsmentioning

confidence: 99%

Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions

Francis

Blount

Corbin

2011

Physiological Reviews

567

546

View full text Add to dashboard Cite

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“…In addition, the oral formulation of iloprost did not show a benefit over placebo in the treatment of RP (23). Phosphodiesterase V inhibition may be useful for the treatment of RP, but further studies are necessary (24,25). Treatment with sildenafil was shown to improve the RCS by 27% compared with placebo in a small crossover study of 18 patients (16 with secondary RP and 2 with primary RP) (25).…”

Section: Discussionmentioning

confidence: 99%

MQX‐503, a novel formulation of nitroglycerin, improves the severity of Raynaud's phenomenon: A randomized, controlled trial

Chung¹,

Shapiro²,

Fiorentino³

et al. 2009

Arthritis & Rheumatism

105

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Objective. Raynaud's phenomenon (RP) affects 3-9% of the general population and >90% of patients with systemic sclerosis. Nitrates are often prescribed for the treatment of RP, but currently available formulations are limited by side effects, particularly headaches, dizziness, and skin irritation. The purpose of this study was to evaluate the tolerability and efficacy of a novel formulation of topical nitroglycerin, MQX-503, in the treatment of RP in an ambulatory setting.Methods. We conducted a multicenter, randomized, placebo-controlled study with a 2-week single-blind run-in period to determine baseline severity, followed by a 4-week double-blind treatment phase. Two hundred nineteen adult patients with a clinical diagnosis of primary or secondary RP received 0.9% MQX-503 gel or matching placebo during the treatment period. Gel was applied immediately before or within 5 minutes of the beginning of an episode of RP (maximum of 4 applications daily). End points included the change in the mean Raynaud's Condition Score (RCS; scale 0-10), the frequency and duration of episodes, and subjective assessments at the target week (the week during the treatment phase that most closely matched the run-in period in terms of ambient temperature) compared with baseline.Results. The mean (%) change in the RCS at the target week compared with baseline was significantly ClinicalTrials.gov identifier: NCT00419419.

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“…Raynaud's disease is characterized by painful temperature-sensitive, digital vasospasms leading to pale, cyanotic skin mostly limited to the digits (Pope 2007). In several clinical studies, sildenafil and vardenafil have been shown to improve peripheral blood flow, decrease the severity of clinical symptoms, and reduce the frequency and cumulative attack duration in some Raynaud's patients (Caglayan et al 2006;Fries et al 2005).…”

Section: Raynaud's Diseasementioning

confidence: 99%

Cyclic GMP-Hydrolyzing Phosphodiesterases

Francis

Corbin

Bischoff

2009

Handbook of Experimental Pharmacology

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Phosphodiesterase Type 5 Inhibition Is a Novel Therapeutic Option in Raynaud Disease

Abstract: Our data indicate that phosphodiesterase type 5 inhibition significantly improves peripheral blood flow and clinical symptoms in a large subset of patients with RD and, thus, may provide a novel therapeutic approach in such individuals.

Cited by 81 publications

References 20 publications

Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions

Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions

MQX‐503, a novel formulation of nitroglycerin, improves the severity of Raynaud's phenomenon: A randomized, controlled trial

Cyclic GMP-Hydrolyzing Phosphodiesterases

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