Designer PDE5 inhibitors, part two

It had been nearly ten years since a PDE5 inhibitor was approved by the U.S. Food and Drug Administration for the treatment of erectile dysfunction in men, but quite recently a new drug was added to the short list of approved drugs for this purpose. [1]

Fig. 1. Structure of avanafil

Stendra is the trade name for the drug avanafil, a relatively new PDE5 inhibitor invented by Mitsubishi Tanabe Pharma Corporation in Japan, licensed in the US by Vivus. [2]

Though it is a PDE5 inhibitor like Viagra, Cialis, and Levitra, Stendra exhibits novel differences that it is claimed make it a safer alternative. It was found to have a better safety profile due, in part, to its increased selectivity among several phosphodiesterases. It is more than 100 times more selective for PDE5 than PDE6 (which is associated with retinal function), and more than 10,000 times more selective for PDE5 than PDE11 (which may be associated with testicular function), an advantage it has over its rivals tadalafil, sildenafil, and vardenafil. [3][4][5][6]
It also appears to be faster-acting than previous PDE5 inhibitors, with most participants in a clinical trial seeing results in under 30 minutes. [7] Tmax (time to peak plasma concentration) was found to be 30 minutes to 1.25 hours (depending on whether participants had just eaten or not); significantly faster than tadalafil (which has a Tmax of 2 hours). [4][8]

Alongside the announcement of a new approved erectile dysfunction medication come more warnings about unapproved medications found in adulterated dietary supplements.

Fig. 2. Structure of aminotadalafil

An analogue of tadalafil (cialis), aminotadalafil differs from tadalafil by the removal of the N2-methyl group and introduction of an amino group.
It is a relatively unstudied drug in regard to it’s pharmacological and toxicological effects, and is not approved for use as a medicine, though it has been identified in a number of “spiked” dietary supplements since 2006. [9][10][11]

The following sexual enhancement products have recently been found to be adulterated with hidden ingredients: [10]

“Instant Hard Rod” contains aminotadalafil
“ZenMaxx” contains aminotadalafil
“RigiRx Plus” contains aminotadalafil
“Boost — Ultra Sexual Enhancement Formula” contains sildenafil
“EreXite” contains tadalafil
“Firminite” contains tadalafil
“Kaboom Action Strips” contains sulfoaildenafil
“VMaxx Rx” contains sulfoaildenafil (this product is subject to a recall by the manufacturer [12])
“X-Rock” contains sildenafil and hydroxythiohomosildenafil
“Mojo Nights” contains tadalafil, sildenafil, sulfoaildenafil, sulfosildenafil, and hydroxythiohomosildenafil

[1] FDA approves Stendra for erectile dysfunction
[2] Vivus press release
[3] BJU Int. 2012 Mar 27
[4] Stendra draft labelling text
[5] International Journal of Impotence Research (2005) 17, 467–468
[6] Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3060-6.
[7] J Sex Med. 2012 Apr;9(4):1122-33
[8] Br J Clin Pharmacol. 2006 March; 61(3): 280–288.
[9] Rapid Commun Mass Spectrom. 2006;20(15):2317-27.
[10] FDA: Tainted Sexual Enhancement Products
[11] Journal of Food and Drug Analysis, Vol. 17, No. 6, 2009, Pages 451-458
[12] FDA: Recalls – The Menz Club, LLC Issues a Voluntary Nationwide Recall of V Maxx Rx due to Undeclared Sulfoaildenafil