029 A novel dopamine reuptake inhibitor, IPED2015 induces spontaneous erections through activation of dopamine receptors in rats

Abstract

Erectile dysfunction where current drugs are insufficient is frequent and new approaches are required to optimize the treatment. The present study investigated whether a newly developed monoamine transport inhibitor, IPED2015 with preference for the dopamine transporter improve erectile function. In male Wistar rats increases in intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured and the ratio ICP/MAP used as a measure of erectile function. It was investigated whether IPED2015 induced erections and whether IPED2015 facilitate suboptimal increases erectile function by electrical stimulation of the cavernosal nerve. Mechanical cutting of the cavernosal nerve and dopamine receptor antagonists were applied to further investigate the mechanism underlying the effects of IPED2015 on erectile function. Microdialysis and locomotor studies were performed in mice. In contrast to vehicle and the 5-hydroxytryptamine reuptake inhibitor, fluoxetine, infusion of IPED2015 (0.1 and 1 mg/kg) increased the number and the duration of spontaneous erections. Section of the proximal cavernosal nerve markedly reduced IPED2015-induced erections. In contrast to the dopamine D1 receptor antagonist, SCH 23390 hydrochloride, the dopamine D2 receptor antagonist, clozapine, decreased magnitude (with 60%) and frequency (with 86%) of IPED2015-induced rises in ICP/MAP. Preinfusion of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil enhanced the magnitude and duration of rises in intracavernosal pressure induced by IPED2015 (0.1 mg/kg). Suboptimal stimulation of the cavernous nerve induced reproducible increases in ICP/MAP that were unchanged in the presence of IPED2015 and IPED2015 plus clozapine. The microdialysis studies showed IPED2015 (10 mg/kg) increased dopamine in cortex and less in striatum compared to noradrenaline and 5-hydroxytrypamine. In locomotor studies 3 mg/kg IPED2015 had no effect, while 10 and 30 mg/kg after 60 min increased distance travelled.