methisosildenafil and Erectile-Dysfunction

To evaluate the efficacy and safety of aildenafil citrate, an oral phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction.. Integrated analyses were made of 8-week, randomized, double-blind, placebo-controlled phase 2 clinical trials involving 250 men with mild-to-severe erectile dysfunction of various etiologies who received aildenafil citrate 30 or 60 mg (n = 167) or placebo (n = 83).. The statistic results of International Index of Erectile Function, Patient Sexual Encounter Profile (SEP) diaries and Global Assessment Question (GAQ) were significantly higher in the aildenafil citrate patients than in the placebo controls. The main drug-related adverse events were flushing, headache, dizziness and naupathia, which were mild and could be self-relieved.. The aildenafil citrate therapy significantly ameliorated erectile function and was well tolerated by a wide range of patients with erectile dysfunction.

Topics: Administration, Oral; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Sulfones; Treatment Outcome

Herbal food supplements, claiming to enhance sexual potency, may contain deliberately added active pharmacological ingredients (APIs) that can be used for the treatment of erectile dysfunction (ED). The aim of this study was to determine whether herbal food supplements on the Dutch market indeed contain APIs that inhibit phosphodiesterase type 5 (PDE-5) inhibitors, such as sildenafil and analogous PDE-5 inhibitors. Herbal food supplements intended to enhance sexual potency (n = 71), and two soft drinks, were sampled from 2003 up to and including 2012. In 23 herbal supplements, nine different PDE-5 inhibitors were identified; in a few cases (n = 3), more than one inhibitor was indentified. The presence of these APIs was however not stated on the label. The concentrations of PDE-5 inhibitors per dose unit were analysed. Furthermore, the potential pharmacologically active properties of the detected PDE-5 inhibitors were estimated by using data from the scientific and patent literature regarding (1) in vitro PDE-5 activity, (2) reported effective doses of registered drugs with PDE-5 inhibitor activity and (3) similarity to other structural analogues. It was concluded that 18 of the 23 herbal food supplements, when used as recommended, would have significant pharmacological effects due to added APIs. Adequate use of existing regulation and control measures seems necessary to protect consumers against the adverse effects of these products.

Topics: Carbonated Beverages; Consumer Product Safety; Dietary Supplements; Erectile Dysfunction; Food Contamination; Food Labeling; Guideline Adherence; Humans; Internet; Legislation, Drug; Legislation, Food; Male; Netherlands; Performance-Enhancing Substances; Phosphodiesterase 5 Inhibitors; Piperazines; Plants, Medicinal; Public Health Surveillance; Purines; Sexual Behavior; Sildenafil Citrate; Sulfones; Vasodilator Agents

A new unapproved analogue of sildenafil was detected in capsules of a herbal dietary supplement promoted as a libido enhancing product. Using LC-DAD-MS, MS-MS, HRMS, IR and NMR the analogue was shown to be a derivative of the PDE-5 inhibitor aildenafil with a nitrosamine moiety. A hydrolysis experiment showed that the new analogue was a prodrug of aildenafil and was therefore named nitroso-prodenafil. A capsule contained 108 mg of nitroso-prodenafil which is equivalent to 84 mg of aildenafil and 5.1 mg of nitrogen monoxide (NO). Although it is unknown how much NO can be usefully generated there is 3-fold more NO present than in a 10 mg isorbide nitrate tablet. Both PDE-5 inhibitors and nitrosamines cause vasodilatation by increasing levels of NO. To their coincidental use is warned against because it may cause a fatal drop in blood pressure. In addition, nitrosamines are known carcinogens. This is the first time a PDE-5 inhibitor and a potential NO donor were identified in one molecule. The findings indicate the dangerous level of advancement in medicinal chemistry by producers of unapproved drugs.

Topics: Designer Drugs; Dietary Supplements; Erectile Dysfunction; Humans; Hydrolysis; Magnetic Resonance Spectroscopy; Male; Molecular Structure; Nitric Oxide Donors; Nitrosamines; Nitrosation; Phosphodiesterase 5 Inhibitors; Piperazines; Prodrugs; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Sulfones; Tandem Mass Spectrometry

We isolated a new illegal sildenafil analogue named mutaprodenafil from a dietary supplement for erectile dysfunction (ED) and proposed that it is an aildenafil derivative containing an imidazole moiety. We subsequently synthesized mutaprodenafil from a thioaildenafil and authenticated its structure.

Topics: Dietary Supplements; Drug Contamination; Erectile Dysfunction; Humans; Imidazoles; Male; Molecular Structure; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

A new analogue of sildenafil was detected in an herbal dietary supplement, which was sold over the internet and promoted as a product for the enhancement of sexual performance. The structure of the compound was established using LC-MS, UV spectroscopy, MS-MS, and NMR. In addition, the compound was cleaved at its sulfonamide S-N bond yielding a sulfonic acid and an amine, which were independently characterized using LC-MS, GC-MS, and derivatization. The compound, named methisosildenafil, is a novel synthetic analogue of sildenafil in which the N-methylpiperazine moiety has been replaced with 2,6-dimethylpiperazine.

Topics: Chromatography, Liquid; Designer Drugs; Dietary Supplements; Erectile Dysfunction; Food Contamination; Humans; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Molecular Structure; Phosphodiesterase Inhibitors; Piperazines; Plant Extracts; Plant Preparations; Purines; Sildenafil Citrate; Spectrophotometry, Ultraviolet; Sulfones