Vardenafil hydrochloride trihydrate

Description

Vardenafil is a potent inhibitor of phosphodiesterase 5 (PDE5; IC₅₀s = 0.2-1.2 nM) and PDE6 (IC₅₀ = 2 nM). It is selective for PDE5 and PDE6 over PDE1 and PDE11 (IC₅₀s = 230 and 130 nM, respectively). Vardenafil (4 mg/kg per day for three weeks) improves erectile function in a rat model of acute arteriogenic erectile dysfunction by increasing intracavernous pressure and mean arterial pressure, and this effect persists for at least two weeks following the end of treatment. Chronic vardenafil administration at a dose of 2 mg/kg for five weeks in subordinate mice reduces the latency to mount and increases the frequency of mounting behavior. Formulations containing vardenafil have been used in the treatment of erectile dysfunction.

Uses

Vardenafil Hydrochloride Trihydrate (cas# 330808-88-3) has therapeutic applications and used in cosmetics and personal care products.

Uses

Vardenafil hydrochloride trihydrate is a potent inhibitor of PDE5 (IC50 = 0.2-1.2 nM) that less effectively blocks the activities of PDE6, PDE1, and PDE11 (IC50s = 2, 230, and 130 nM, respectively). PDE5 inhibitors, including vardenafil, have applications in several conditions, including erectile dysfunction, pulmonary arterial hypertension, and lower urinary tract dysfunction.[Cayman Chemical]

Biological Activity

Vardenafil HCl Trihydrate (BAY38-9456) is a new type PDE inhibitor with IC50 of 0.7 and 180 nM for PDE5 and PDE1, respectively.

in vitro

Vardenafil specifically inhibits the hydrolysis of cGMP by PDE5 with an IC50 of 0.7 nM (6.6 nM). Vardenafil significantly enhances the SNP-induced relaxation of human trabecular smooth muscle at 3 nM (10 nM). Vardenafil also significantly potentiates both ACh-induced and transmural electrical stimulation-induced relaxation of trabecular smooth muscle. Vardenafil (100 mM) increases cyclic GMP levels in rat hippocampal slices. Vardenafil, tadalafil, and Sildenafil each competitively inhibit cGMP hydrolysis by phosphodiesterase-5 (PDE5), thereby fostering cGMP accumulation and relaxation of vascular smooth muscle.

in vivo

Vardenafil dose-dependently potentiates erectile responses to intravenously administered sodium nitroprusside in rabbit. Vardenafil (3 mg/kg, p.o.) results in an improved object discrimination performance in rats. Vardenafil (30 mg/L, p.o.) increases both iNOS and proliferating cell nuclear antigen expression (SM cell replication) in rats, with normalization of the dynamic infusion cavernosometry drop rate and SM/collagen ratio.Vardenafil induces powerful preconditioning-like cardioprotective effect against ischemia/reperfusion injury through opening of mitochondrial K(ATP) channels in the heart of rabbit. Vardenafil protects the ischemic myocardium against reperfusion injury through a mechanism dependent on mitochondrial K(ATP) channel opening.

IC 50

PDE5: 0.7 nM (IC₅₀); PDE6: 11 nM (IC₅₀); PDE1: 180 nM (IC₅₀); PDE3: >1000 nM (IC₅₀); PDE4: >1000 nM (IC₅₀)

References

[1] saenz de tejada i1, angulo j, cuevas p, fernández a, moncada i, allona a, lledó e, körschen hg, niewöhner u, haning h, pages e, bischoff e.the phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new pde5 inhibitor vardenafil. int j impot res. 2001 oct;13(5):282-90.