Effect of Acute Dapoxetine Administration on the Pudendal Motoneuron Reflex in Anesthetized Rats: Comparison With Paroxetine

Purpose

Pudendal motoneuron reflex discharges elicited by bilateral electrical stimulation of the dorsal nerves of the penis were used as an experimental model of the expulsion reflex of ejaculation to investigate the effect of acute intravenous delivery of dapoxetine, a short acting selective serotonin reuptake inhibitor, in anesthetized rats. Dapoxetine was compared with paroxetine, the selective serotonin reuptake inhibitor of reference.

Materials and Methods

Stimulating electrodes were placed bilaterally on the dorsal nerves of the penis and a recording electrode was placed on the motor branch of the pudendal nerve to monitor pudendal motoneuron reflex discharges in urethane anesthetized rats. Pudendal motoneuron reflex discharges induced by penile dorsal nerve stimulation were measured before and 60 minutes after a single intravenous injection of dapoxetine or paroxetine, each tested at 3 doses (1, 3 and 10 mg/kg) or after a single injection of vehicle.

Results

At all doses tested dapoxetine significantly lengthened the latency of pudendal motoneuron reflex discharges following bilateral stimulation of the dorsal nerves of the penis in comparison with vehicle, whereas only the 1 mg/kg dose of paroxetine was effective. The amplitudes of pudendal motoneuron reflex discharges were significantly decreased only in rats treated with 3 mg/kg dapoxetine compared to vehicle.

Conclusions

Acute systemic delivery of selective serotonin reuptake inhibitors is capable of modulating the expulsion reflex of ejaculation in anesthetized rats with dapoxetine appearing to be more effective than paroxetine. These findings support the beneficial effect of on-demand administration of dapoxetine for premature ejaculation.

Key Words: penis, ejaculation, dapoxetine, paroxetine, motor neurons

Abbreviations and Acronyms: 5-HT, 5-hydroxytryptamine, BS, bulbospongiosus, DNP, dorsal nerve of penis, IV, intravenous, LPGi, lateral part of PGi, PE, premature ejaculation, PGi, paragigantocellularis nucleus, PMRD, pudendal motoneuron reflex discharge, SSRI, selective serotonin reuptake inhibitor