LY 266097 hydrochloride

LY266097 hydrochloride is a selective 5-HT2B receptor antagonist with pKis of 7.7, 9.8, and 7.6 for 5-HT2A, 5-HT2B, 5-HT2C, respectively. 5-HT2B receptor blockade contributes to the research in depression[1].

Research Areas >> Inflammation/Immunology

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

5-HT2B Receptor:9.8 (pKi)

5-HT2A Receptor:7.7 (pKi)

5-HT2C Receptor:7.6 (pKi)

LY266097 is a highly selective 5-HT2B receptor antagonist with a pKi of 9.7 for the human cloned 5-HT2B receptor and a 100-fold greater selectivity over human 5-HT2C and 5-HT2A sites[2].

LY266097 (0.6 mg/kg for 2-day administration) rescues Escitalopram-induced decrease in dopamine (DA) [1]. The administration of LY266097 alone or its addition on the last 3 days of a 14-day Escitalopram regimen increases pyramidal neuron firing and burst activity[1]. Animal Model: Male Sprague-Dawley rats weighing 250-350 g[1] Dosage: 0.6 mg/kg Administration: Administered i.p. alone or concomitantly with Escitalopram (2 mg/kg) for 2 days Result: Short-term administration (0.6 mg/kg/day for 2 days; i.p.) alone had no effect on these parameters, its co-administration counteracted the inhibitory effect of escitalopram on the firing activity of DA neurons, resulting in a recovery to control level.

[1]. Rami Hamati, et al. Serotonin-2B receptor antagonism increases the activity of dopamine and glutamate neurons in the presence of selective serotonin reuptake inhibition. Neuropsychopharmacology. 2020 Nov;45(12):2098-2105.

[2]. Luc Maroteaux, et al. New therapeutic opportunities for 5-HT 2 receptor ligands. Pharmacol Ther. 2017 Feb;170:14-36.