Differential effects of serotonin reuptake inhibitors on erectile responses, NO‐production, and neuronal NO synthase expression in rat corpus cavernosum tissue

Increased incidence of impotence is associated with some selective serotonin‐reuptake‐inhibitors (SSRIs), but the pathophysiological mechanism is unknown. Paroxetine and citalopram are extensively used SSRIs, but only paroxetine has been shown to inhibit nitric oxide synthase (NOS) activity. NO is a key mediator of penile erection. Thus, the aim of this study was to determine the effects of paroxetine and citalopram on erectile function and NO production, in a rat model. Application of cavernosal nerve electrical stimulation produced frequency‐related intracavernosal pressure (ICP) increases, which were inhibited by the NOS inhibitor, NG‐nitro‐L‐arginine (0.3 mg kg−1). Acute or chronic (2 weeks) paroxetine‐treatment (10 mg kg−1) reduced ICP‐responses, while citalopram did not. Paroxetine, but not citalopram, significantly reduced nitrite+nitrate plasma levels by 61.4% and inhibited penile neuronal NOS (nNOS) protein expression by 31.2% after chronic treatment. The results show that paroxetine inhibits erectile responses in rats. We propose that this effect is due to reduced NO production and nNOS expression. British Journal of Pharmacology (2001) 134, 1190–1194; doi:10.1038/sj.bjp.0704351