Brief Description

MK-4305 is a potent antagonist of OX1 receptor and OX2 receptor with Ki values of 0.55 nM and 0.35 nM, respectively.
Orexins/hypocretins are key neuropeptides responsible for regulating central arousal and reward circuits. Two receptors respond to orexin signaling, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) with partially overlapping nervous system distributions. As a dual orexin receptor (OXR) antagonist (DORA), suvorexant (MK-4305) has shown promise for the treatmen to finsomnias and sleep disorders.
In vitro: In vitro study showed that MK-4305 possesseed a clean ancillary profile (>10000-fold selectivity for OX2R) as determined by an MDS Pharma off-target screen of 170 enzymes, receptors, and ion channels.
In vivo: In a mice in-vivo study, suvorexant (25mg/kg) was tested in mice during the inactive phase (lights on) when sleep is naturally more prevalent and when orexin levels are normally low. It was found that suvorexant substantially disturbed the sleep architecture by selectively increasing REM during the first 4h after dosing. At the doses tested, suvorexant significantly decreased wake only during the first hour and IPSU did not affect wake time. These data suggest that OX2R preferring antagonists may have areduced tendency for perturbing NREM/REM architecture in comparison with DORAs.
Clinical trial: Suvorexant (trade name Belsomra) is marketed by Merck & Co. for the treatment of insomnia. It is effective for insomnia, at least for four weeks and as compared to a placebo. It was approved for sale by the U.S. Food & Drug Administration on August 13, 2014. The United States DEA has placed it on the list of schedule IV controlled substances. The drug became available in the United States on Tuesday, 3 February 2015 and Japan somewhere in November 2014 (http://en .wikipedia.org/wiki/Suvorexant).

Solubility

DMSO 10 mg/ml; Water <1 mg/ml

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

White to off-white solid