Nitrosoprodenafil is a synthetic designer drug found in "herbal" aphrodisiac products, which is a novel nitrosated analogue of

sildenafil Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is unclear if it is effective for treating sexual dysfunction in women. It is taken by ...

(Viagra). It has an innovative structure which acts as a

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

, breaking down in the body to release both the PDE₅ inhibitor aildenafil as well as free

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...

, which have powerfully synergistic effects. This dual mechanism of action has never been exploited by conventional pharmaceutical companies because of the risks involved; usually combining PDE₅ inhibitors with nitric oxide releasers like amyl nitrite is contraindicated as it can cause a precipitous drop in blood pressure that can potentially result in death.

Nitrosamine In organic chemistry, nitrosamines (or more formally ''N''-Nitrosamines) are organic compounds with the chemical structure , where R is usually an alkyl group. They feature a nitroso group () bonded to a deprotonated amine. Most nitrosamines are ...

s are also generally avoided in drug development as they can often be

hepatotoxic Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fro ...

and carcinogenic, so while the combined mechanisms of action are likely to be effective, this drug also has severe risks of toxicity. Shortly after Venhuis et al. published the suggested structure for nitrosoprodenafil, it was contested by Demizu et al. who suggested the structure was an azathioprine/aildenafil hybrid. This newly suggested structure was dubbed 'mutaprodenafil' because of the structural similarity with the mutagenic azathioprine. The final confirmation of the azathioprine/aildenafil hybrid was provided by Sakamoto et al. who prepared crystals for X-ray analysis. Although Sakamoto et al. support the name 'mutaprodenafil', they prefer to use 'nitrosoprodenafil' instead.

References

{{Phosphodiesterase inhibitors Designer drugs Nitroso compounds PDE5 inhibitors Phenol ethers Piperazines Pyrazolopyrimidines Thiazoles Propyl compounds

See also

References