Acetildenafil

Last updated
Acetildenafil
Acetildenafil.svg
Clinical data
MedlinePlus a699015
Routes of
administration
By mouth
ATC code
  • None
Legal status
Legal status
  • US:Unapproved and unscheduled
Identifiers
  • 5-[2-Ethoxy-5-[2-(4-ethyl-piperazin-1-yl)-acetyl]-phenyl]-1-methyl-3-propyl-1,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
Formula C25H34N6O3
Molar mass 466.586 g·mol−1
3D model (JSmol)
  • CCCc1nn(C)c3c1nc([nH]c3=O)-c2cc(ccc2OCC)C(=O)CN4CCN(CC)CC4
  • InChI=1S/C25H34N6O3/c1-5-8-19-22-23(29(4)28-19)25(33)27-24(26-22)18-15-17(9-10-21(18)34-7-3)20(32)16-31-13-11-30(6-2)12-14-31/h9-10,15H,5-8,11-14,16H2,1-4H3,(H,26,27,33) Yes check.svgY
  • Key:RRBRQNALHKQCAI-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Acetildenafil (hongdenafil) is a synthetic drug which acts as a phosphodiesterase inhibitor. [1] It is an analog of sildenafil (Viagra) [2] which has been detected in numerous different brands of "herbal aphrodisiac" products sold in convenience stores that claim to boost libido and alleviate erectile dysfunction. [3]

A range of designer analogs of licensed PDE5 inhibitors such as sildenafil and vardenafil have been detected in recent years in over-the-counter herbal aphrodisiac products, [4] [5] [6] [7] in an apparent attempt to circumvent both the legal restrictions on sale of erectile dysfunction drugs, which are prescription-only medicines in most Western countries, and the patent protection which allows sale of these drugs by competitors only with permission from the patent holders (typically, under a license from the inventors) and to introduce efficacy into otherwise ineffective herbal products. These compounds have been demonstrated to display PDE5 inhibitory activity in vitro and presumably have similar effects when consumed, but have undergone no formal testing in either humans or animals, and as such may represent significant health risks to consumers of these products due to their unknown safety profile. [3] [8] Attempts to ban such ingredients have not been successful for the most part, many jurisdictions having laws restricting chemical analogs but only those of narcotics and doping agents. However, at least one court case has resulted in a product being taken off the market. [9]

See also

Related Research Articles

Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men. Through its connection to self-image and to problems in sexual relationships, erectile dysfunction can cause psychological harm.

<span class="mw-page-title-main">Sildenafil</span> Drug for erectile dysfunction and hypertension

Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is also sometimes used off-label for the treatment of certain symptoms in secondary Raynaud's phenomenon. It is unclear if it is effective for treating sexual dysfunction in women. It can be taken orally, intravenously, or sublingually. Onset when taken orally is typically within twenty minutes and lasts for about two hours.

<span class="mw-page-title-main">Phosphodiesterase</span> Class of enzymes

A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases, as well as numerous less-well-characterized small-molecule phosphodiesterases.

<span class="mw-page-title-main">Tadalafil</span> Medication used to treat erectile dysfunction

Tadalafil, sold under the brand name Cialis among others, is a medication used to treat erectile dysfunction, benign prostatic hyperplasia, and pulmonary arterial hypertension. It is taken by mouth. Onset is typically within half an hour and the duration is up to 36 hours.

<span class="mw-page-title-main">Vardenafil</span> Chemical compound

Vardenafil, sold under the brand name Levitra among others, is a medication that is used for treating erectile dysfunction. It is a PDE5 inhibitor. It is taken by mouth.

<span class="mw-page-title-main">Yohimbine</span> Chemical compound

Yohimbine, also known as quebrachine, is an indole alkaloid derived from the bark of the African tree Pausinystalia johimbe; also from the bark of the unrelated South American tree Aspidosperma quebracho-blanco. Yohimbine is an α2-adrenergic receptor antagonist, and has been used in a variety of research projects. It is a veterinary drug used to reverse sedation in dogs and deer.

<span class="mw-page-title-main">PDE5 inhibitor</span> Vasodilating drug

A phosphodiesterase type 5 inhibitor is a vasodilating drug that works by blocking the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic GMP in the smooth muscle cells lining the blood vessels supplying various tissues. These drugs dilate the corpora cavernosa of the penis, facilitating erection with sexual stimulation, and are used in the treatment of erectile dysfunction (ED). Sildenafil was the first effective oral treatment available for ED. Because PDE5 is also present in the smooth muscle of the walls of the arterioles within the lungs, two PDE5 inhibitors, sildenafil and tadalafil, are FDA-approved for the treatment of pulmonary hypertension. As of 2019, the wider cardiovascular benefits of PDE5 inhibitors are being appreciated.

cGMP-specific phosphodiesterase type 5 Mammalian protein found in Homo sapiens

Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina. It has also been recently discovered to play a vital role in the cardiovascular system.

<span class="mw-page-title-main">Udenafil</span> Chemical compound

The drug udenafil is marketed under the trade name Zydena. It is within the PDE5 inhibitor class (which also includes avanafil, sildenafil, tadalafil, and vardenafil). Like other PDE5 inhibitors, it is used to treat erectile dysfunction. Udenafil was developed by Dong-A Pharmaceutical. It has fairly rapid onset of action (peak plasma concentration after 1 to 1.5 hours), and has long duration of action (plasma half-life of 11 to 13 hours). Udenafil's pharmacokinetics allows once-daily dosage (in addition to on-demand use). Typical doses are 100 and 200 mg. Udenafil is available in Korea, Russia, and the Philippines. It has not yet been approved for use in the United States by the U.S. Food and Drug Administration.

<span class="mw-page-title-main">Avanafil</span> Chemical compound

Avanafil is a PDE5 inhibitor approved for erectile dysfunction by the FDA on April 27, 2012 and by EMA on June 21, 2013. Avanafil is sold under the brand names Stendra and Spedra. It was invented at Mitsubishi Tanabe Pharma, formerly known as Tanabe Seiyaku Co., and licensed to Vivus Inc., which partnered with Menarini Group to commercialise Spedra in over forty European countries, Australia, and New Zealand. Metuchen Pharmaceuticals obtained exclusive rights within the United States.

<span class="mw-page-title-main">Herbal viagra</span> A class of herbal products said to treat erectile dysfunction

Herbal viagra is a herbal product advertised as treating erectile dysfunction. Many different products are advertised as herbal viagra, but with varying ingredients. No clinical trials or scientific studies support the effectiveness of any of these ingredients for the treatment of erectile dysfunction and some products have been found to contain drugs and other adulterants, and have been the subject of FDA and FTC warnings and actions to remove them from the market.

<span class="mw-page-title-main">Lodenafil</span> Chemical compound

Lodenafil is a drug belonging to a class of drugs called PDE5 inhibitor, which many other erectile dysfunction drugs such as sildenafil, tadalafil, and vardenafil also belong to. Like udenafil and avanafil it belongs to a new generation of PDE5 inhibitors.

<span class="mw-page-title-main">Mirodenafil</span> Chemical compound

Mirodenafil belongs to the drug class PDE5 inhibitors, which includes avanafil, sildenafil, tadalafil, udenafil, and vardenafil, and is the first-line treatment for erectile dysfunction. Developed by SK Chemicals Life Science, mirodenafil is marketed in Korea under the trade name Mvix, offered both as tablets and as orally dissolving film.

<span class="mw-page-title-main">Sulfoaildenafil</span> Chemical compound

Sulfoaildenafil (thioaildenafil) is a synthetic drug that is a structural analog of sildenafil (Viagra). It was first reported in 2005, and it is not approved by any health regulation agency. Like sildenafil, sulfoaildenafil is a phosphodiesterase type 5 inhibitor.

<span class="mw-page-title-main">Aildenafil</span> Chemical compound

Aildenafil (methisosildenafil) is a synthetic drug that is a structural analog of sildenafil (Viagra). It was first reported in 2003, and it is not approved by any health regulation agency. Like sildenafil, aildenafil is a phosphodiesterase type 5 inhibitor.

<span class="mw-page-title-main">Nitrosoprodenafil</span> Chemical compound

Nitrosoprodenafil is a synthetic designer drug found in "herbal" aphrodisiac products, which is a novel nitrosated analogue of sildenafil (Viagra). It has an innovative structure which acts as a prodrug, breaking down in the body to release both the PDE5 inhibitor aildenafil as well as free nitric oxide, 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. Nitrosamines are also generally avoided in drug development as they can often be hepatotoxic and carcinogenic, so while the combined mechanisms of action are likely to be effective, this drug also has severe risks of toxicity.

Phosphodiesterases (PDEs) are a superfamily of enzymes. This superfamily is further classified into 11 families, PDE1 - PDE11, on the basis of regulatory properties, amino acid sequences, substrate specificities, pharmacological properties and tissue distribution. Their function is to degrade intracellular second messengers such as cyclic adenine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which leads to several biological processes like effect on intracellular calcium level by the Ca2+ pathway.

<span class="mw-page-title-main">Benzamidenafil</span> Chemical compound

Benzamidenafil or xanthoanthrafil is a synthetic drug that acts as a PDE5 inhibitor. It has the same mechanism of action as pharmaceutical drugs used to treat erectile dysfunction, but it is not approved by any regulatory agency for such use. It has been found as an undeclared adulterant in supposedly "natural" health supplements. In 2009, the supplement manufacturer Hi-Tech Pharmaceuticals recalled its product Stamina-Rx because it was adulterated with benzamidenafil.

<span class="mw-page-title-main">Homosildenafil</span> Chemical compound

Homosildenafil is a synthetic drug which acts as a phosphodiesterase inhibitor. It is an analog of sildenafil and vardenafil. Homosildenafil was first identified as an adulterant in sex enhancement products in 2003 and was more recently detected in dietary supplements.

<span class="mw-page-title-main">Desmethylsibutramine</span> Chemical compound

Desmethylsibutramine is an active metabolite of the anorectic drug sibutramine. It is a more potent monoamine reuptake inhibitor than sibutramine and has been sold as an ingredient in weight loss products sold as dietary supplements, along with related compounds such as the N-ethyl and 3,4-dichloro derivatives.

References

  1. "Acetildenafil". Cayman Chemical. Retrieved 26 Mar 2017.
  2. Blok-Tip L, Zomer B, Bakker F, Hartog KD, Hamzink M, Ten Hove J, et al. (August 2004). "Structure elucidation of sildenafil analogues in herbal products". Food Additives and Contaminants. 21 (8): 737–48. doi:10.1080/02652030412331272467. hdl: 10029/11381 . PMID   15370823. S2CID   45568769.
  3. 1 2 Poon WT, Lam YH, Lai CK, Chan AY, Mak TW (October 2007). "Analogues of erectile dysfunction drugs: an under-recognised threat". Hong Kong Medical Journal = Xianggang Yi Xue Za Zhi. 13 (5): 359–63. PMID   17914141.
  4. Venhuis BJ, de Kaste D (October 2012). "Towards a decade of detecting new analogues of sildenafil, tadalafil and vardenafil in food supplements: a history, analytical aspects and health risks". Journal of Pharmaceutical and Biomedical Analysis. 69: 196–208. doi:10.1016/j.jpba.2012.02.014. PMID   22464558.
  5. Zou P, Oh SS, Hou P, Low MY, Koh HL (February 2006). "Simultaneous determination of synthetic phosphodiesterase-5 inhibitors found in a dietary supplement and pre-mixed bulk powders for dietary supplements using high-performance liquid chromatography with diode array detection and liquid chromatography-electrospray ionization tandem mass spectrometry". Journal of Chromatography A. 1104 (1–2): 113–22. doi:10.1016/j.chroma.2005.11.103. PMID   16364350.
  6. Gratz SR, Gamble BM, Flurer RA (2006). "Accurate mass measurement using Fourier transform ion cyclotron resonance mass spectrometry for structure elucidation of designer drug analogs of tadalafil, vardenafil and sildenafil in herbal and pharmaceutical matrices". Rapid Communications in Mass Spectrometry. 20 (15): 2317–27. Bibcode:2006RCMS...20.2317G. doi: 10.1002/rcm.2594 . PMID   16817245.
  7. Hou P, Zou P, Low MY, Chan E, Koh HL (September 2006). "Structural identification of a new acetildenafil analogue from pre-mixed bulk powder intended as a dietary supplement". Food Additives and Contaminants. 23 (9): 870–5. doi:10.1080/02652030600803856. PMID   16901855. S2CID   35240702.
  8. Oh SS, Zou P, Low MY, Koh HL (November 2006). "Detection of sildenafil analogues in herbal products for erectile dysfunction". Journal of Toxicology and Environmental Health. Part A. 69 (21): 1951–8. doi:10.1080/15287390600751355. PMID   16982533. S2CID   40831895.
  9. Venhuis BJ, Blok-Tip L, de Kaste D (May 2008). "Designer drugs in herbal aphrodisiacs". Forensic Science International. 177 (2–3): e25-7. doi:10.1016/j.forsciint.2007.11.007. PMID   18178354.