DA-8159, a new PDE5 Iihibitor, induces penile erection in conscious and acute spinal cord injured rabbits.

Abstract

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. 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. 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. 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.