5-HT receptors (Serotonin receptors) are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous systems. Type: 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, 5-HT7. They mediate both excitatory and inhibitory neurotransmission. Serotonin elicits its effects on sleep and waking by interacting with the seven major families of 5-HT receptors. Among them, the 5-HT7 receptor has been cloned from mouse, rat, guinea-pig and human and the receptor binding profile is consistent across species and between cloned and native 5-HT7 receptors. Moreover, 5-HT7 receptors couple positively to adenylyl cyclase when expressed in cell lines. In brain tissue from various species, 5-HT7 receptor mRNA is discretely localized within thalamus, hypothalamus, limbic and cortical regions.
SB-269970 is a potent, selective and brain-penetrant 5-HT7 receptor antagonist. In addition, SB-269970 is also a potent inhibitor of [3H]-5-CT binding to guinea-pig cerebral cortex membranes. This compound inhibits 5-CT-stimulated adenylyl cyclase activity in guinea-pig hippocampal membranes. In guinea-pigs, SB-269970 blocks 5-CT-induced hypothermia. At the same time, in conscious rats, SB-269970 significantly reduces time spent in Paradoxical Sleep (PS) during the first 3 h of EEG recording. David R Thomas et al. have confirmed that SB-269970 can bind to human 5-HT7A receptors expressed in HEK293 cell membranes (h5-HT7A/293). Furthermore, SB-269970 binds saturably and apparently monophasically to both h5-HT7A/293 and guinea-pig cortex membranes.
To sum up, SB-269970 is a potent, selective and brain-penetrant 5-HT7 receptor antagonist, and has the potential for neurological research.