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Ejaculatory responses are inhibited by a new chemical entity, DA-8031, in preclinical rodent models of ejaculation.

Abstract：

OBJECTIVE:To investigate the efficacy of DA-8031, a novel compound for the treatment of premature ejaculation (PE), we performed in vivo pharmacological studies using 2 preclinical animal models, electrical stimulation of sensory branch of pudendal nerve (SBPdn) and para-chloroamphetamine (PCA)-induced ejaculation model. METHODS:First of all, in electrical stimulation of an SBPdn model, an SBPdn in the pelvic canal of the spinal cord transected from rats was identified. Then an electromyogram (EMG) of the bulbospongiosus (BS) muscle was recorded during electrical stimulation of SBPdn after single intravenous (IV) dosing of DA-8031 and its reference drug, dapoxetine. In the second model, both seminal vesicle pressure (SVP) and the EMG profile of the BS muscle were recorded in PCA-induced ejaculation animals after treated with the same dosing regimen. RESULTS:Area under the curve (AUC) of the BS muscle by EMG wave exhibited a significant reduction in the DA-8031 and dapoxetine 3 mg/kg treated groups, and maximum amplitudes were also significantly decreased in DA-8031 1, 3 mg/kg and dapoxetine 3 mg/kg dose level in the SBPdN stimulation model. Consistent with these findings, in a PCA-induced ejaculation model, SVP increase was significantly inhibited from DA-8031 0.3 mg/kg dose level, and AUC of BS muscle EMG significantly decreased in the DA-8031 1, 3 mg/kg groups. CONCLUSION:The present study implied that DA-8031 contributed to an effective co-coordinated inhibition of the expulsion phase of ejaculation by modulating BS muscle activity and the emission phase through blocking SVP rise. From these findings, DA-8031 is further expected to have clinical efficacy in human studies.

journal_name

Urology

journal_title

Urology

authors

Kang KK,Ahn GJ,Sung JH,Kim SH,Kim H,Lee S

doi

10.1016/j.urology.2012.12.006

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

920.e13-8

issue

4

eissn

0090-4295

issn

1527-9995

pii

S0090-4295(12)01478-1

journal_volume

81

pub_type

杂志文章

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