DA-8159, a new PDE5 Iihibitor, induces penile erection in conscious and acute spinal cord injured rabbits.
OBJECTIVE
DA-8159 is a pyrazolopyrimidinone derivative showing potent and selective phosphodiesterase 5 (PDE5) inhibition. In the previous study, DA-8159 induced a dose-dependent increase in the intracavernous pressure (ICP) in anaesthetized dogs. The aim of this study was to investigate the effects of DA-8159 on penile erection in conscious and acute spinal cord injured (ASCI) rabbits.


METHODS
DA-8159 was given orally (0.3 to 10mg/kg) to normal rabbits and ASCI rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion. The erection was evaluated in a time-course manner by measuring the length of the uncovered penile mucosa in the absence or presence of intravenous sodium nitroprusside (SNP), a nitric oxide (NO) donor.


RESULTS
DA-8159 induced a dose-dependent penile erection in both the conscious and ASCI rabbits. The efficacy of DA-8159 was potentiated and the effective doses were significantly decreased by an intravenous injection of SNP. Potentiation of the effect by a nitric oxide donor implies that DA-8159 can enhance the erectile activity during sexual arousal.


CONCLUSIONS
These results demonstrate that DA-8159 may be a useful treatment option for erectile dysfunction in patients with or without a spinal cord injury, but further evaluation of the effects of DA-8159 on humans must be performed.
Kang
Kyung Koo
KK
Research Laboratories of Dong-A Pharmaceutical Company, 47-5 Sanggal, Kiheung, Youngin, Kyunggi, 449-900 South Korea. kangkk@donga.co.kr
Ahn
Gook Jun
GJ
Ahn
Byoung Ok
BO
Yoo
M
M
Kim
Won Bae
WB
D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D009562:Nissl Bodies / Q000473:pathology; D010410:Penile Erection / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines; D011817:Rabbits; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C419664:udenafil; D000096926:Benzenesulfonamides