RS130-180

RS130-180, also known as N--2,5-dimethoxy-4-phenethylamine, is a β-arrestin-biased serotonin 5-HT_2A receptor agonist of the phenethylamine, 2C, and NBOMe families. It is the NBOMe derivative in which the phenyl ring has an N,''N-dimethylamino substitution at the 4 position and the 2-position methoxy group on the benzyl ring has been replaced with a propynyloxy group.
The drug favors activation of β-arrestin signaling over G_q signaling. RS130-180 is said to be useful for in-vitro studies, but to have suboptimal pharmacokinetic properties for in-vivo use. β-Arrestin-biased serotonin 5-HT_2A receptor agonists do not produce the head-twitch response in rodents and it is thought that they may be non-hallucinogenic in humans. The cryo-EM structures of the serotonin 5-HT_2A receptor with RS130-180, as well as with various serotonergic psychedelics, have been solved and published by Bryan Roth and colleagues.
RS130-180 was first described in the literature by 2022. It was derived from an earlier compound called ZINC000341335936, which was identified via in-silico'' screening of 1.6billion molecules for serotonin 5-HT_2A receptor agonism with AlphaFold2. RS130-180 was developed via structural modification of ZINC000341335936 by David E. Nichols and colleagues.