The penile erection efficacy of a new phosphodiesterase type 5 inhibitor, mirodenafil (SK3530), in rabbits with acute spinal cord injury.
Mirodenafil (SK3530) is a new potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5). Recent clinical trials have demonstrated that mirodenafil is an effective treatment for erectile dysfunction. Its mechanism of action is enhancement of nitric oxide (NO) induced cGMP formation resulting in significant relaxation of the corpus cavernosum (CC). The aim of this study was to investigate the oral efficacy of mirodenafil in an acute spinal cord-injured rabbit model. Mirodenafil or sildenafil citrate was given orally to male rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion spinal cord injury (SCI). Erections were evaluated in a time-course manner by measuring the length of the uncovered penile mucosa. In the transection SCI model, penile erections were induced at 0.3, 1 and 3 mg/kg of mirodenafil but sildenafil only showed an erectile response at 3 mg/kg. The effects of 1 and 3 mg/kg of mirodenafil were significantly increased by intravenous injection of sodium nitroprusside (SNP), a nitric oxide donor. In the ischemic-reperfusion injury model, 3 mg/kg of either mirodenafil or sildenafil produced a penile erection response. After injection of SNP, the lengths of immediate penile erections were significantly increased in the 1 and 3 mg/kg mirodenafil and 3 mg/kg sildenafil groups. The onset of erectile activity was faster with mirodenafil than with sildenafil citrate. These results demonstrate that mirodenafil may be useful for treating erectile dysfunction in patients with a spinal cord injury.
Jung
Ji-Youn
JY
Department of Companion and Laboratory Animal Science, Kongju National University, Yesan.
Kim
Sang-Ki
SK
Kim
Byeong-Soo
BS
Lee
Seung-Ho
SH
Park
Young-Seok
YS
Kim
So-Jung
SJ
Choi
Changsun
C
Yoon
Seong-Il
SI
Kim
Jong-Suk
JS
Cho
Sung-Dae
SD
Im
Gwang-Jin
GJ
Lee
Soo-Min
SM
Jung
Ji-Won
JW
Lee
Yong-Soon
YS
D000284:Administration, Oral; D000818:Animals; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors; D011744:Pyrimidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D013119:Spinal Cord Injuries / Q000150:complications*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*
D058986:Phosphodiesterase 5 Inhibitors; D011744:Pyrimidinones; D013449:Sulfonamides; C528396:mirodenafil