title: YKP1447, A Novel Potential Atypical Antipsychotic Agent.
abstract: (S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-HT(2A), Ki=0.61 nM, 5-HT(2C), Ki=20.7 nM) and dopamine (D(2), Ki=45.9 nM, D(3), Ki=42.1 nM) receptors with over 10~100-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing (ED(50)=0.93 mg/kg) and DOI-induced head twitch (ED(50)=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine (ED(50)=0.54 mg/kg) and the avoidance response (ED(50)=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose (ED(50)=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.
authors.affiliation: Life Science Division, SK Holdings Co., Ltd., Daejeon 305-712, Korea.
authors.forename: Seon Min
authors.initials: SM
authors.lastname: Dong
authors.forename: Yong Gil
authors.initials: YG
authors.lastname: Kim
authors.forename: Joon
authors.initials: J
authors.lastname: Heo
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Ji
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Cho
authors.forename: Byong Sung
authors.initials: BS
authors.lastname: Kwak