Oral Naftidrofuryl

Abstract

Naftidrofuryl has been used for the treatment of intermittent claudication, a symptom of mild to moderate peripheral occlusive arterial disease (POAD), for at least 2 decades. As a serotonin 5-HT2 receptor antagonist, naftidrofuryl has vasoactive properties in addition to its favourable effects on oxidative metabolism, peripheral transcutaneous oxygen pressure and the rheological properties of platelets and erythrocytes. The drug may also reduce hypercholesterolaemia-induced intimal proliferation. Clinical trials which conform best with European guidelines have shown that 3 and 6 months' oral therapy with naftidrofuryl 600 or 633 mg/day (in 3 or 2 divided doses) increased pain-free walking distance to a greater extent than placebo administration in patients with POAD. Surgical revascularisation was required less often during 6 months of therapy with naftidrofuryl than in placebo recipients, confirming the superiority of naftidrofuryl treatment compared with placebo. Available data provide some evidence of efficacy of the drug in the treatment of ischaemic rest pain and vascular ulceration. However, further trials are required before the usefulness of oral naftidrofuryl in severe POAD can be fully established. When given orally, naftidrofuryl is well tolerated. Mild gastrointestinal effects are the most common adverse events, requiring withdrawal of therapy in approximately 1.2% of patients compared with 0.95% of placebo-treated patients. In summary, oral naftidrofuryl improves the symptoms of intermittent claudication in patients with POAD with minimal risk of adverse effects. Therefore, in patients with Fontaine's classification stage II POAD for whom lifestyle modifications and management of concomitant disease have provided insufficient benefit, naftidrofuryl is potentially useful.

Multiplicity of Equilibrium States in Separating Stereoisomeric Mixtures of Nafronyl Oxalate by Crystallization

“…It is used for the treatment of vascular diseases, including intermittent claudication, stroke, and dementia. 37,38 The isomer having (2S,2′R) configuration contributes most to the therapeutic efficacy. 36 In our recent study, we have developed a procedure for isolating the most active stereoisomer, (2S,2′R), from a raw material that was a quaternary stereoisomeric mixture enriched with the racemate (2R,2′S)/(2S,2′R).…”

Development of a Route to the Most Active Nafronyl Stereoisomer by Coupling Asymmetric Synthesis and Chiral Chromatography Separation

“…Nafronyl oxalate is a vasodilator used for the treatment of intermittent claudication, stroke or dementia. It possesses 5‐hydroxytryptamine 2 (5‐HT 2 ) receptor antagonist activity 1–4. Nafronyl molecule is characterized by two stereogenic centers and it is marketed in the form of oxalate salt as a mixture of four stereoisomers with the absolute configuration as follows: (2 R ,2′ R ), (2 R ,2′ S ), (2 S ,2′ S ), and (2 S ,2′ R ).…”

Separation of Stereoisomeric Mixtures of Nafronyl as a Representative of Compounds Possessing Two Stereogenic Centers By Coupling Crystallization, Diastereoisomeric Conversion and Chromatography

“…It is used in medicine in the form of oxalate salt for the treatment of vascular diseases, including intermittent claudication, stroke, and dementia. The pharmacological properties of nafronyl have been described in detail by Goldsmith and Wellington and Barradell and Broqden …”

“…It is used in medicine in the form of oxalate salt for the treatment of vascular diseases, including intermittent claudication, stroke, and dementia. The pharmacological properties of nafronyl have been described in detail by Goldsmith and Wellington 18 and Barradell and Broqden. 19 Due to the existence of two stereogenic centers in the position 2 of the propionic acid backbone and in the position 2′ of the tetrahydrofuryl carbon atom, the molecule has four stereoisomers; i.e., it forms two racemates which comprise enantiomeric pairs: 20 (2R,2′R):(2S,2′S) and (2R,2′S):(2S,2′R).…”