title: 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.
  
  
  CONCLUSIONS
  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.
authors: Research Institute of Dong-A Pharmaceutical company, 47-5 Sang-gal, Ki-heung, Yong-in, Kyoung-gi, 446-905, South Korea. kangkk@donga.co.kr
authors: Kyung Koo
authors: KK
authors: Kang
authors: Gook Jun
authors: GJ
authors: Ahn
authors: Ji Hyun
authors: JH
authors: Sung
authors: Soon Hoe
authors: SH
authors: Kim
authors: Hyunah
authors: H
authors: Kim
authors: Sukhyang
authors: S
authors: Lee
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004542:Ejaculation / Q000187:drug effects*; D004558:Electric Stimulation; D004576:Electromyography; D008297:Male; D010413:Penis / Q000187:drug effects* / Q000294:innervation; D061686:Premature Ejaculation / Q000188:drug therapy*; D060525:Pudendal Nerve; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001572:Benzofurans; D017367:Selective Serotonin Reuptake Inhibitors; C559089:DA 8031