A novel small molecule fluorescent agent called SERTlight specifically labels serotonin neurons in the mammalian brain. SERTlight is a substrate for the serotonin transporter (SERT) and accumulates inside serotonin neurons, producing a bright and selective optical signal. Unlike many other agents, SERTlight does not activate serotonin receptors or other common targets and is not released by neuronal activity or drugs like MDMA. It is compatible with other imaging tools and can label distant axonal projections while allowing simultaneous measurement of serotonin release. This new tool enables detailed study of the serotonin system in health and disease.
Ibogaine and its main metabolite noribogaine inhibit the vesicular monoamine transporter 2 (VMAT2) with submicromolar potency, as shown in cell-based assays and two-photon microscopy of mouse brain synaptic vesicle clusters. Noribogaine also induces partial serotonin release from synaptic vesicles and binds VMAT2 at a distinct site from the established inhibitor dihydrotetrabenazine. These compounds additionally inhibit plasma membrane monoamine transporters, prominently the serotonin transporter (SERT), and a novel target, organic cation transporter 2 (OCT2). Several iboga analogs display dual inhibition of VMAT2 and SERT with comparable potencies, termed "Synaptic Reuptake Inhibitors" (SynRIs). This profile explains why ibogaine and noribogaine do not induce catalepsy, unlike other VMAT2 inhibitors, and illustrates the complex "matrix pharmacology" of iboga compounds.