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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ahn
Gook Jun
GJ
Research Institutes, Dong-A Pharmaceutical Company, Kiheung, Youngin, Kyunggi, South Korea. ahnsnu2@donga.co.kr
Kang
Kyung Koo
KK
Kim
Dong Sung
DS
Ahn
Byoung Ok
BO
Kim
Won Bae
WB
Kang
Sung Keun
SK
Lee
Byeong Chun
BC
Hwang
Woo Suk
WS
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D019540:Area Under Curve; D001794:Blood Pressure; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000139:chemically induced / Q000188:drug therapy*; D005473:Fluoxetine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007275:Injections, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D017374:Paroxetine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010410:Penile Erection / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D011312:Pressure; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D005473:Fluoxetine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017374:Paroxetine; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D011743:Pyrimidines; D017367:Selective Serotonin Reuptake Inhibitors; D013449:Sulfonamides; C517384:Pde5a protein, rat; C419664:udenafil; D000096926:Benzenesulfonamides