PUDAFENSINE, A MONOAMINE REUPTAKE INHIBITOR, PROMOTES PARACOPULATORY BEHAVIORS AND INCREASES GENITALIA FLOW IN FEMALE RATS

Female sexual dysfunction associated with distress is common and there are limited treatment options. Pudafensine (IP2015), a monoamine-reuptake inhibitor with a preference for the dopamine transporter, has improved erectile function in male rats (doi:10.1111/bph.16362) and patients. We hypothesized that pudafensine would promote sexual behavior and increase blood flow in female rat genitalia.

Female Sprague–Dawley (12-15 week) rats synchronized in estrous (cloprostenol 250 μg/kg at the 0 and 3rd day) were treated with a single dose of apomorphine, pudafensine and vehicle, and sexual behavior was evaluated. Estrogen (E2) and Follicle Stimulating Hormone (FSH) were measured by ELISA. Another group of similar rats was anesthetized with pentobarbital, two Laser Doppler probes measured blood flow in the clitoris and vagina, and genital resistance arteries were isolated for myograph experiments. Electrical field stimulation (EFS) was applied to stimulate the cavernous nerve to the clitoris to confirm specific flow-measured changes.

The sexual encounter profile showed apomorphine had effects similar to the vehicle, while pudafensine (10 mg/Kg) increased paracopulatory behaviors (darts and hops). E2 and FSH levels were similar to physiological ranges. In the second group of rats, vehicle, and increasing doses of pudafensine were infused in the jugular vein. EFS of the clitoral nerve increased blood flow in the clitoral area. In contrast to vehicle infusion, increasing doses of pudafensine dose-dependently increased clitoral blood flow, while vaginal blood flow was unaltered. Pudafensine concentration-dependently relaxed isolated genital resistance arteries.

Our findings show that the monoamine reuptake inhibitor, pudafensine, increased paracopulatory sexual behaviors. Pudafensine, like the physiological stimulation of the nerve, leads to increased blood flow in the clitoral area and isolated arteries. Further studies will be required to clarify whether the effect of pudafensine can translate into improved treatment of women with sexual dysfunction.

Ulf Simonsen is CSO and Simon Comerma Steffensen both has shares of Initiator Pharma A/S, part of the research was funded by the company.