DA-8159 reverses selective serotonin reuptake inhibitor-induced erectile dysfunction in rats

• Published in: Urology (Ridgewood, N.J.) N.J.), 2005, Vol.65 (1), p.202-207
• Main Authors: Ahn, Gook Jun, Kang, Kyung Koo, Kim, Dong Sung, Ahn, Byoung Ok, Kim, Won Bae, Kang, Sung Keun, Lee, Byeong Chun, Hwang, Woo Suk
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Area Under Curve; Biological and medical sciences; Blood Pressure; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Evaluation, Preclinical; Electric Stimulation; Erectile Dysfunction - chemically induced; Erectile Dysfunction - drug therapy; Fluoxetine - antagonists & inhibitors; Fluoxetine - toxicity; Injections, Intravenous; Male; Medical sciences; Nephrology. Urinary tract diseases; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Paroxetine - antagonists & inhibitors; Paroxetine - toxicity; Penile Erection - drug effects; Phosphodiesterase Inhibitors - pharmacology; Phosphodiesterase Inhibitors - therapeutic use; Phosphoric Diester Hydrolases - drug effects; Pressure; Pyrimidines - administration & dosage; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Rats; Rats, Sprague-Dawley; Serotonin Uptake Inhibitors - antagonists & inhibitors; Serotonin Uptake Inhibitors - toxicity; Sulfonamides
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2004.09.023

To assess the efficacy of the phosphodiesterase 5 inhibitor, DA-8159, in selective serotonin reuptake inhibitor (SSRI)-induced rat erectile dysfunction model by measuring intracavernous pressure (ICP). Erectile dysfunction was induced by oral administration of either paroxetine or fluoxetine in rats. The changes in ICP and mean arterial pressure (MAP) were simultaneously recorded throughout electrostimulation of the cavernous nerve with 2 or 10 Hz after intravenous injection of DA-8159 (1 mg/kg). Statistical analysis was performed on the ICP/MAP ratio and the area under the curve of the ICP/MAP ratio. Although the reduction in the ICP responses after acute paroxetine or fluoxetine administration was statistically significant, the electrical stimulation of the cavernous nerve induced a statistically significant, frequency-dependent increase in the ICP/MAP ratio after DA-8159 administration. The differences in the ICP/MAP ratio and corresponding area under the curve values from the SSRI-treated group were statistically significant. The results of the present study have demonstrated that DA-8159 reverses the decrease in ICP induced by SSRI treatment, suggesting that DA-8159 may be a potential therapeutic agent for the treatment of erectile dysfunction associated with the use of SSRIs.