Valby, Denmark and Tokyo, Japan, 10 October 2013, 2013-10-10 09:15 CEST (GLOBE NEWSWIRE) —
•The clinical program in Alzheimer’s disease is planned to include approximately 3,000 patients from several countries worldwide
•Lu AE58054 is a selective 5-HT6 receptor antagonist under investigation for the treatment of Alzheimer’s disease[i]
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Lu AE58054 is a potent and selective 5-HT6 receptor antagonist under development by Lundbeck as an augmentation therapy for the treatment of cognitive deficits associated with Alzheimer’s disease and schizophrenia. As of February 2010 it is in phase II clinical trials.
- Lundbeck expands its pipeline – initiating phase II clinical trials with a new compound for the treatment of schizophrenia
- Lundbeck initiates clinical phase II trials with Lu AE58054 as augmentation treatment in Alzheimer’s disease
Lu AE58054 Hydrochloride M.Wt: 434.83
Lu AE58054 Hydrochloride Formula: C20H20ClF5N2O
Lu AE58054 Hydrochloride Storage: at -20℃ 2 years
Lu AE58054 Hydrochloride CAS No.: 467458-02-2
Description: IC50 Value: 0.83 nm Lu AE58054 is an in-vitro potency and selectivity, in-vivo binding affinity and effect of the 5-HT(6)R antagonist. in 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. 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. Clinical trial: Lu-AE58054 Added to Donepezil for the Treatment for Moderate Alzheimer’s Disease. Phase2
References on Lu AE58054 Hydrochloride:
. Arnt J, Bang-Andersen B, Grayson B, Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats. Int J Neuropsychopharmacol. 2010 Sep;13(8):1021-33.
. Witten L, Bang-Andersen B, Nielsen SM, Characterization of [?H]Lu AE60157 ([?H]8-(4-methylpiperazin-1-yl)-3-phenylsulfonylquinoline) binding to 5-hydroxytryptamine? (5-HT?) receptors in vivo.Eur J Pharmacol. 2012 Feb 15;676(1-3):6-11.