Alprostadil for the treatment of impotence

Hanchanale, Vishwanath; Eardley, Ian

doi:10.1517/14656566.2014.873789

Cited by 47 publications

(31 citation statements)

References 50 publications

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“…6B). This is important because PGE 1 and its analogs are currently used in the clinical practice as vasodilators in multiple situations, including erectile dysfunction, patent ductus arteriosus or intermittent claudication (Talosi et al, 2004;Swainston Harrison and Plosker, 2007;Nakanishi et al, 2008;Hanchanale and Eardley, 2014) . To get insight into the nature of the interaction between PGE 2 and AKR1B1, we performed MALDI-TOF MS analysis (Fig.…”

Section: Resultsmentioning

confidence: 99%

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

Díez-Dacal¹,

Sánchez‐Gómez

Sánchez‐Murcia

et al. 2015

Mol Pharmacol

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Aldose reductase (AKR1B1) is a critical drug target because of its involvement in diabetic complications, inflammation, and tumorigenesis. However, to date, development of clinically useful inhibitors has been largely unsuccessful. Cyclopentenone prostaglandins (cyPGs) are reactive lipid mediators that bind covalently to proteins and exert anti-inflammatory and antiproliferative effects in numerous settings. By pursuing targets for modification by cyPGs we have found that the cyPG PGA 1 binds to and inactivates AKR1B1. A PGA 1 -AKR1B1 adduct was observed, both by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry and by SDS-PAGE using biotinylated PGA 1 (PGA 1 -B). Insight into the molecular interactions between AKR1B1 and PGA 1 was advanced by molecular modeling. This anticipated the addition of PGA 1 to active site Cys298 and the potential reversibility of the adduct, which was supported experimentally. Indeed, loss of biotin label from the AKR1B1-PGA 1 -B adduct was favored by glutathione, indicating a retro-Michael reaction, which unveils new implications of cyPG-protein interaction. PGA 1 elicited only marginal inhibition of aldehyde reductase (AKR1A1), considered responsible for the severe adverse effects of many AKR1B1 inhibitors. Interestingly, other prostaglandins (PGs) inhibited the enzyme, including non-electrophilic PGE 1 and PGE 2 , currently used in clinical practice. Moreover, both PGA 1 and PGE 1 reduced the formation of sorbitol in an ex-vivo model of diabetic cataract to an extent comparable to that attained by the known AKR inhibitor epalrestat. Taken together, these results highlight the role of PGs as AKR1B1 inhibitors and the interest in PG-related molecules as leads for the development of novel pharmacological tools.

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Section: Resultsmentioning

confidence: 99%

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

Díez-Dacal¹,

Sánchez‐Gómez

Sánchez‐Murcia

et al. 2015

Mol Pharmacol

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“…These drugs are injected into cavernous bodies. There are also attempts to use prostacyclin analogues in the form of intraurethral insert or topical drug administration in the form of ointment [37].…”

Section: Treatmentmentioning

confidence: 99%

“…Leki te wstrzykuje się do ciał jamistych. Czynione są też próby stosowania analogów prostacykliny w postaci wkładek docewkowych lub podawania leku miejscowo jako maść [37]. U chorych, u których wspomniane leki nie są skuteczne zaleca się próżniowe pompki powodujące napływ krwi do ciał jamistych.…”

Section: Badania Czynnościowe Układu Naczyniowego U Chorych Na Twardzunclassified

Erectile dysfunctions in patients with systemic sclerosis

Chrzanowska¹,

Kucharz

2019

Forum Reumatologiczne

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Erectile dysfunctions are a common feature in patients with systemic sclerosis. They are resulted from a complex pathomechanism. The main role is attributed to vascular alterations and fibrosis of the carvernous bodies. Depression and disturbed autonomy nervous system function may be additional factors for development of erectile dysfunctions. Diagnosis is based on subjective patient's data and functional tests. Treatment of erectile dysfunctions in scleroderma patients is difficult, multifactorial and sometimes ineffective.

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“…However, the role of topical alprostadil is now being reconsidered, especially in the treatment of ED in diabetic patients for whom oral PDE5is therapy is ineffective. Recent phase III trials produced positive results leading to the approval of topical alprostadil in Canada [134]. A recent review confirmed intraurethral alprostadil to be an effective second-line treatment with higher acceptance and compliance rates than other treatments.…”

Section: Other Treatments For Ed In Diabetesmentioning

confidence: 99%

Erectile dysfunction and its management in patients with diabetes mellitus

Defeudis

Gianfrilli

Emidio

et al. 2015

Rev Endocr Metab Disord

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Diabetes can be described as a syndrome of multiple closely related conditions induced by a chronic state of hyperglycaemia resulting from defective insulin secretion, insulin action or both. Chronic complications associated with diabetes (including neuropathy, vascular disease, nephropathy and retinopathy) are common, and of these, erectile dysfunction (ED) deserves special attention. ED and its correlation with cardiovascular disease require careful evaluation and appropriate treatment. PDE5 inhibitors (PDE5is) are an important tool for the treatment of ED, with new drugs coming onto the market since the late 90s. This review offers an overview of PDE5is and their use in treating ED in diabetes. We underline the differences between different types of PDE5i, focusing on available doses, duration of action, T ½, side effects and selectivity profiles in relation to patients with diabetes. We also discuss the link between diabetes and ED in presence of various associated cofactors (obesity, hypertension and its pharmacological treatments, atherosclerosis, hyperhomocysteinaemia, neuropathy, nephropathy, hypogonadism and depression). Finally a number of past and ongoing clinical trials on the use of PDE5is in patients with diabetes are presented to offer an overview of the appropriate treatment of ED in this condition.

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Alprostadil for the treatment of impotence

Cited by 47 publications

References 50 publications

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

Erectile dysfunctions in patients with systemic sclerosis

Erectile dysfunction and its management in patients with diabetes mellitus

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Alprostadil for the treatment of impotence

Cited by 47 publications

References 50 publications

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA1 and Clinically Used Prostaglandins

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA1 and Clinically Used Prostaglandins

Erectile dysfunctions in patients with systemic sclerosis

Erectile dysfunction and its management in patients with diabetes mellitus

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Product

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Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins