Candidate molecule for premature ejaculation, DA-8031: in vivo and in vitro characterization of DA-8031.
OBJECTIVE
To evaluate the efficacy of DA-8031 against premature ejaculation, we performed in vitro and in vivo pharmacologic studies.


METHODS
We used a monoamine transporter binding affinity assay, receptor binding affinity assay, monoamine reuptake inhibition assay, and serotonin uptake inhibition assay in platelets and chemically induced ejaculation models in rats.


RESULTS
The present study reports on the pharmacologic profile of the putative antipremature ejaculation drug, DA-8031. DA-8031 exhibits high affinity and selectivity to the serotonin transporter (Ki value 1.94 nM for 5-hydroxytryptamine transporter, 22 020 nM for norepinephrine transporter, and 77 679 nM for dopamine transporter) and potency to inhibit serotonin reuptake into the rat brain synaptosome in vitro (half maximal inhibitory concentration 6.52 nM for 5-hydroxytryptamine, 30.2 μM for norepinephrine, and 136.9 μM for dopamine). In the platelet serotonin uptake study, DA-8031 exhibited significant inhibition at oral doses of 10 and 30 mg/kg in a dose-dependent manner. In the sexual response studies, after oral and intravenous administration of DA-8031, ejaculation was significantly inhibited in both para-chloroamphetamine- and meta-chlorophenylpiperazine-mediated ejaculation models in rats.


CONCLUSIONS
The pharmacologic profiles observed in the present study suggest the potential for DA-8031 as a therapeutic agent useful in the treatment of premature ejaculation.
Research Laboratory, Dong-A Pharmaceutical Company, Giheung, Yongin, Gyeonggi, Korea.
Hyung-Jun
HJ
Jeon
Hae-Sun
HS
Kim
Chan-Ho
CH
Lee
Young-Gun
YG
Lee
Seol-Min
SM
Choi
Yong-Sung
YS
Sohn
Chang-Yong
CY
Shin
Junghoon
J
Kim
Hyun-Joo
HJ
Shim
Kyung-Koo
KK
Kang
Byoung-Ok
BO
Ahn
Soon-Hoe
SH
Kim
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004542:Ejaculation; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012735:Sexual Dysfunction, Physiological / Q000188:drug therapy*; D027981:Symporters / Q000378:metabolism
D001572:Benzofurans; D050483:Dopamine Plasma Membrane Transport Proteins; D014179:Neurotransmitter Uptake Inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D027981:Symporters; C559089:DA 8031