Samelisant (SUVN-G3031) is a potent and selective histamine H3 receptor (H3R) inverse agonist with good brain penetration and oral bioavailability. Samelisant has a similar binding affinity towards human (hH3R; K i =8.7 nM) and rat (rH3R;K i =9.8 nM) H3R indicating no inter-species differences. Samelisant can be used for the research of sleep-related disorders.
In Vitro
Samelisant displays inverse agonist activity and it exhibits very high selectivity towards H3R. The pEC 50 value of histamine (8.5) for human H3 receptor increases to 8.2, 7.3 and 6.2 after treatment with 1, 10 and 100 nM of Samelisant, respectively. The pEC 50 value of histamine (8.2) for rat H3 receptor increases to 7.9, 7.4 and 6.4 after treatment with 1, 10 and 100 nmol/L of Samelisant, respectively. Samelisant binds to the orthosteric site in a reversible manner with K b values of 1.3 nM and 1.1 nM deduced from pA 2 value for human and rat H3R, respectively. Samelisant also modulates dopamine and norepinephrine levels in the cerebral cortex while it has no effects on dopamine levels in the striatum or nucleus accumbens. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Treatment with Samelisant (10 and 30 mg/kg, p.o.) produces a significant increase in wakefulness with a concomitant decrease in non-rapid eye movement sleep (NREM) sleep in orexin knockout mice subjected to sleep electroencephalography (EEG) . Samelisant also produces a significant decrease in direct rapid eye movement (REM) sleep onset (DREM) episodes, demonstrating its anticataplectic effects in an animal model relevant to narcolepsy . Samelisant treatment in mice produces a dose-dependent increase in tele -methylhistamine levels indicating the activation of histaminergic neurotransmission . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male Wistar rats or male C57BL6J mice Dosage: 1, 3, 10, and 30 mg/kg Administration: Oral administration Result: Produced a dose-dependent increase in t-MH levels in the frontal cortex, hypothalamus and cerebrospinal fluid (CSF) of male Wistar rats.\nProduced a significant increase in t-MH levels of the frontal cortex, striatum and hypothalamus in mice.
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