SB-200646

SB-200646 is the first selective 5-HT2B/2C over 5-HT2A receptor antagonist with pKi values of 7.5, 6.9 and 5.2 for 5-HT2B, 5-HT2C and 5-HT2A, respectively. SB-200646 is orally active and has electrophysiological and anxiolytic properties in vivo[1][2].

Research Areas >> Neurological Disease

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

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

5-HT2B Receptor:7.5 (pKi)

5-HT2C Receptor:6.9 (pKi)

5-HT2A Receptor:5.2 (pKi)

SB-200646 (4 μM) abolishes the ethanol-induced increase in miniature inhibitory postsynaptic current (mIPSC) frequency and had no effect on basal mIPSC frequency[1].

SB-200646A (20 mg/kg; intravenous injection; daily; for 21 days; male albino Sprague-Dawley rats) treatment significantly decreases the number of spontaneously active ventral tegmental area (VTA) dopaminergic neurons[1]. The i.v. administration of 4-16 mg/kg of SB-200646A significantly increases the firing rate and % events as bursts in spontaneously active VTA dopaminergic neurons and significantly increases the % events as burst in substantia nigra pars compacta (SNC) dopaminergic neurons[1]. Animal Model: Male albino Sprague-Dawley rats (200-225 g at the beginning of treatment and 300-350 g at the time of the experiment)[1] Dosage: 20 mg/kg Administration: Intravenous injection; daily; for 21 days Result: Significantly decreased the number of spontaneously active ventral tegmental area (VTA) dopaminergic neurons.

[1]. Blackburn TP, et al. The acute and chronic administration of the 5-HT(2B/2C) receptor antagonist SB-200646A significantly alters the activity of spontaneously active midbrain dopamine neurons in the rat: An in vivo extracellular single cell study. Synapse. 2006 Jun 15;59(8):502-12.

[2]. Kennett GA, et al. In vivo properties of SB 200646A, a 5-HT2C/2B receptor antagonist. Br J Pharmacol. 1994 Mar;111(3):797-802.

[3]. Theile JW, et al. Role of 5-hydroxytryptamine2C receptors in Ca2+-dependent ethanol potentiation of GABA release onto ventral tegmental area dopamine neurons. J Pharmacol Exp Ther. 2009 May;329(2):625-33.