RS130-180, also known as N-(2-propargyloxy)-2,5-dimethoxy-4-(dimethylamino)phenethylamine, is a ò-arrestin-biased serotonin 5-HT<sub>2A</sub> 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 ò-arrestin signaling over G<sub>q</sub> signaling. RS130-180 is said to be useful for in-vitro studies, but to have suboptimal pharmacokinetic properties for in-vivo use. ò-Arrestin-biased serotonin 5-HT<sub>2A</sub> 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<sub>2A</sub> 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<sub>2A</sub> receptor agonism with AlphaFold2. RS130-180 was developed via structural modification of ZINC000341335936 by David E. Nichols and colleagues.