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GPCR/G ProteinNeuronal Signaling-
Lu AE58054???5-HT6????????????????????????????????????????????????????????????Ki???0.83 nM???
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生物活性
Description
Lu AE58054 is an in-vitro potency and selectivity, in-vivo binding affinity and effect of the 5-HT(6)R antagonist with a Ki value of 0.83 nM.IC50 Value: 0.83 nm[1]Target: 5-HT(6)Rin vitro: Lu AE58054 displayed high affinity to the human 5-HT(6) receptor (5-HT(6)R) with a Ki of 0.83 nm. In a 5-HT(6) GTPgammaS efficacy assay Lu AE58054 showed no agonist activity, but demonstrated potent inhibition of 5-HT-mediated activation. Besides medium affinity to adrenergic alpha(1A)- and alpha(1B)-adrenoreceptors, Lu AE58054 demonstrated >50-fold selectivity for more than 70 targets examined[1].in vivo: Orally administered Lu AE58054 potently inhibited striatal in-vivo binding of the 5-HT(6) antagonist radioligand [(3)H]Lu AE60157, with an ED(50) of 2.7 mg/kg. Steady-state modelling of an acute pharmacokinetic/5-HT(6)R occupancy time-course experiment indicated a plasma EC(50) value of 20 ng/ml. Administration of Lu AE58054 in a dose range (5-20 mg/kg p.o.) leading to above 65% striatal 5-HT(6)R binding occupancy in vivo, reversed cognitive impairment in a rat novel object recognition task induced after subchronic treatment for 7 d with phencyclidine (PCP 2 mg/kg b.i.d., i.p. for 7 d, followed by 7 d drug free). The results indicate that Lu AE58054 is a selective antagonist of 5-HT(6)Rs with good oral bioavailability and robust efficacy in a rat model of cognitive impairment in schizophrenia[1].Clinical trial: Lu-AE58054 Added to Donepezil for the Treatment for Moderate Alzheimer's Disease. Phage2
Clinical Trial
H. Lundbeck A/S
Healthy
April 2015
Phase 1
H. Lundbeck A/S
Healthy
March 2015
Phase 1
H. Lundbeck A/S
Alzheimer's Disease
April 2014
Phase 3
H. Lundbeck A/S
Alzheimer Disease
January 2015
Phase 1
H. Lundbeck A/S
Bioequivalence
September 2016
Phase 1
H. Lundbeck A/S
Healthy Volunteers
May 2015
Phase 1
H. Lundbeck A/S
Healthy
December 2013
Phase 1
H. Lundbeck A/S
Healthy Volunteers
March 2014
Phase 1
H. Lundbeck A/S
Heptic Impairment
July 2014
Phase 1
H. Lundbeck A/S-Otsuka Pharmaceutical Co., Ltd.
Alzheimer's Disease
March 2014
Phase 3
H. Lundbeck A/S-Otsuka Pharmaceutical Co., Ltd.
Alzheimer's Disease
February 2014
Phase 3
H. Lundbeck A/S-Otsuka Pharmaceutical Co., Ltd.
Alzheimer's Disease
October 2013
Phase 3
H. Lundbeck A/S
Schizophrenia-Cognition
November 2008
Phase 2
H. Lundbeck A/S
Alzheimer's Disease
December 2009
Phase 2
H. Lundbeck A/S
Healthy
July 2013
Phase 1
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References
