Nortadalafil

Uses

A N-desmethyl analogue of the human PDE5 inhibitor Tadalafil (T004500). A potential antiplasmodial drug.

Biological Activity

the cgmp-specific pde5 is the major pde isozyme in the corpus cavernosum, and controls penile erection. the pde5 inhibitors used in the clinic amplify the no-ccmp pathway and enhance the normal process leading to penile erection.nortadalafil is demethyl tadalafil, which is a pde5 inhibitor currently marketed in pill form for treating erectile dysfunction under the name cialis and for the treatment of pulmonary arterial hypertension under the name adcirca.

in vitro

tadalafil has been identified as a highly potent pde5 inhibitor (ic50 = 5 nm) with high selectivity for pde5 vs pde1-4 and pde6. it displays 85-fold greater selectivity vs pde6 than sildenafil [1].

in vivo

tadalafil showed profound and long-lasting blood pressure lowering activity (30 mmhg/>7 h) in the spontaneously hypertensive rat model after oral administration (5 mg/kg) [1].

target

PDE5

IC 50

n/a for nortadalafil; 5 nm for tadalafil

References

[1] daugan a, grondin p, ruault c, le monnier de gouville ac, coste h, linget jm, kirilovsky j, hyafil f, labaudinière r. the discovery of tadalafil: a novel and highly selective pde5 inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione analogues. j med chem. 2003;46(21):4533-42.
[2] porst h, hell-momeni k, büttner h. chronic pde-5 inhibition in patients with erectile dysfunction - a treatment approach using tadalafil once-daily. expert opin pharmacother. 2012 jul;13(10):1481-94. doi: 10.1517/14656566.2012.693162.