Design and synthesis of optical and pharmacological probes for studying serotonergic system

Serotonin (5HT) is a monoamine neurotransmitter that modulates a wide range of brain functions via the actions at 5HT receptors and 5HT transporters. Dysregulation of 5HT transmission underlies many neurological and psychiatric disorders, such as depression and anxiety disorders. To advance the research in serotonergic neurotransmission and dysfunction, we have focused on two distinct approaches- 1) investigation of basic biology of synaptic function and 2) small molecule drug discovery. We have first developed a novel fluorescent tracer of 5HT, providing a molecular tool to study the serotonergic system in the CNS with subcellular and cellular resolution in vitro and in vivo. Next, we have developed novel small molecules to activate the serotonin 2A receptor (5HT2A agonists). By exploring new scaffolds, we expect to expand the pharmacophore space for 5HT2A agonists to allow exploration of 5HT2A as molecular target for treating neuropsychiatric disorders, and guide structure-based discovery of more selective 5HT2A agonists with desirable pharmacological properties as potential drug candidates.