A pilot double-blind randomized placebo-controlled study of molsidomine 16�mg once-a-day in patients suffering from stable angina pectoris: correlation between efficacy and over time plasma concentrations

Messin, R; Fenyvesi, T; Carreer-Bruhwyler, Fabienne; Crommen, Jacques; Chiap, Patrice; Hubert, Philippe; Dubois, Claude; Famaey, Jean-Pierre; Géczy, Joseph

doi:10.1007/s00228-003-0597-z

Cited by 13 publications

(6 citation statements)

References 15 publications

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“…Furthermore, these drugs have not been combined systemically, or topically for the treatment of chronic pain. However, as single drugs, α 2 A receptor agonists, NO donors or PDE inhibitors have been used systemically to treat pain associated with angina, [28][29][30] peripheral arterial disease 31,32 and neuropathic pain, [33][34][35] indicating their usefulness in these syndromes. PA inhibitors share the vasodilator, 36 antiischemic 37 and antiplatelet aggregation 38 effects of PDE inhibitors, but their added antioxidant, 39 anticytokine, 40 antileukocyte attractant, 41 immunosuppressant, 42 and mitochondrial protective 43 effects suggest they may be more effective at relieving chronic pain.…”

Section: Introductionmentioning

confidence: 99%

Topical Combinations to Treat Microvascular Dysfunction of Chronic Postischemia Pain

Laferrière

Abaji

Tsai³

et al. 2014

Anesthesia &Amp; Analgesia

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Section: Introductionmentioning

confidence: 99%

Topical Combinations to Treat Microvascular Dysfunction of Chronic Postischemia Pain

Laferrière

Abaji

Tsai³

et al. 2014

Anesthesia &Amp; Analgesia

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“…However, a significant body of evidence exists in the literature with regard to pharmacological therapy for stable angina (see Table 1). [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] The choice of additional medication over and above first-line treatment (with either a beta-blocker or calcium channel antagonist) follows the rationale for chronic stable angina -i.e. it is considered on an individual patient basis, taking into account age, heart rate, blood pressure, the presence of diabetes mellitus or impaired renal function and tolerability.…”

Section: Pharmacological Therapiesmentioning

confidence: 99%

Management of Refractory Angina Pectoris

Cheng¹,

Sainsbury²,

Fisher³

et al. 2016

European Cardiology Review

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Refractory angina (RA) is conventionally defined as a chronic condition (≥3 months in duration) characterised by angina in the setting of coronary artery disease (CAD), which cannot be controlled by a combination of optimal medical therapy, angioplasty or bypass surgery, and where reversible myocardial ischaemia has been clinically established to be the cause of the symptoms. 1 In clinical practice, patients diagnosed with RA are a heterogeneous group; common among them, however, is that they remain significantly limited by persistent debilitating chest discomfort despite optimised conventional therapy. In many cases, functional imaging may not demonstrate myocardial ischaemia. It is important to recognise that irrespective of aetiology, patients with refractory chest discomfort often attribute their symptoms to be cardiac in origin and believe that they may herald a life-threatening cardiac event. This predisposes to a progressive decline in their mental wellbeing and increasing anxiety whereby pain begets pain. Consequently, patients can develop persistent symptoms and pessimistic health beliefs, translating to negative behaviours and an impaired quality of life. In this regard, a shift in our approach of RA to that of managing a 'chronic chest pain syndrome' may help us not only to better appreciate the multifactorial aetiologies that are in operation in any given patient but also encourage the use of a holistic approach to manage these patients more effectively. Epidemiology Precise estimates of the prevalence and incidence of RA are not available; however, several sources suggest that this is a large and growing problem. 2,3 Variations in definition and clinical heterogeneity of patients labelled with a diagnosis of RA significantly complicate such endeavours. Data from the Canadian Community Health Survey (2000-2001) suggest that ~500,000 Canadians are living with unresolved angina. 4 The proportion of these patients with true RA is unknown. 5 In the US, it is estimated that between 600,000 and 1.8 million patients have RA, with approximately 75,000 new cases diagnosed each year. 5,6 In Europe, the annual incidence of RA is estimated at 30,000-50,000 new cases per year. 1,7 Specific figures for the UK are lacking and further work to define the burden of RA in the UK population is needed. However, if the results shown by Williams et al., who found that 6.7 % of patients undergoing angiography in a contemporary cohort had no revascularisation option, are applied to the 247,363 angiograms performed in England in 2014, it can be estimated that ~16,500 new cases of RA may occur in England per year. 3,8 Given improvements in CAD-related survival and increasing age of the population, together with an increasing appreciation from the contemporary Outcome of Percutaneous Coronary Intervention for Stent ThrombosIs Multicentre Study (OPTIMIST) registry that the long term prognosis of RA is not as bad as previously thought, the incidence and prevalence of RA is only set to rise. 5,6,9,10 Furthermore, it has also been r...

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“…Furthermore, these agents have neither been combined systemically, nor combined in topical preparations for the treatment of chronic pain. However, α 2A receptor agonists, NO donors and PDE inhibitors have been used systemically in patients or preclinical animal models to treat pain associated with angina 13,43,66 , PAD 19,52,82 , CRPS 18,40,63,74 , neuropathic pain 32,53,60 and PDN 16,24,48,84 indicating their usefulness in these syndromes. PA inhibitors have not been used to treat chronic pain, but should be equally or more effective than PDE inhibitors since they have anti-oxidant 7,34 , anticytokine 68,76 , anti-chemotaxic 70,91 , immunosuppressant 15,23 , and mitochondrial protective 12 effects, in addition to the vasodilator 61 , anti-ischemic 90 and anti-platelet aggregation 62 effects they share with PDE inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain

Ragavendran

Laferrière

Xiao

et al. 2013

The Journal of Pain

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Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α 2 -adrenergic (α 2A ) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent anti-allodynic effects in rats with chronic post- CIHR Author ManuscriptCIHR Author Manuscript CIHR Author Manuscript ischemia pain, and the anti-allodynic dose-response curves of PDE and PA inhibitors were shifted 2.5-10 fold leftward when combined with non-analgesic doses of α 2A receptor agonists or NO donors. Topical combinations also produced significant anti-allodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 h after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α 2A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain.Perspective-This article presents the synergistic anti-allodynic effects of combinations of α 2A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected areas.

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A pilot double-blind randomized placebo-controlled study of molsidomine 16�mg once-a-day in patients suffering from stable angina pectoris: correlation between efficacy and over time plasma concentrations

Cited by 13 publications

References 15 publications

Topical Combinations to Treat Microvascular Dysfunction of Chronic Postischemia Pain

Topical Combinations to Treat Microvascular Dysfunction of Chronic Postischemia Pain

Management of Refractory Angina Pectoris

Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain

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