ZINC000443438219 (also known as Z0443438219 or '8219) is a piperazine derivative which acts as a potent and selective serotonin reuptake inhibitor (SSRI). It was developed as an elaborated hit from an ultra-large-scale docking screen, looking for molecules which would bind to the orthosteric site of the serotonin transporter (SERT) in the extracellular-closed, inward-open state favored by compounds such as ibogaine, noribogaine, and MDMA, as opposed to the outward-open conformation favored by compounds such as cocaine and conventional SSRI antidepressants like fluoxetine or citalopram. (R)-'8219 binds to SERT with a binding affinity (Ki) of 3nM and produced antidepressant- and anxiolytic-like effects in animal studies, while the (S) enantiomer '8221 was also active but with a much weaker Ki of 170nM. The drug is not a substrate-type serotonin releasing agent. '8219 was first described in the scientific literature by Bryan L. Roth and colleagues in 2023.
See also Substituted piperazine Z3517967757 Z8526711350 Z8779877149
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