Pharmacologic control of neurotransmitter transporters

CNS diseases including anxiety disorders, depression, ADHD, and Parkinson’s, etc. have often been linked to abnormalities in neurotransmitter transport, and not surprisingly, drugs such as Prozac, Paxil and Mirapex have been developed to correct the resulting imbalances in neurotransmitter levels. We have discovered a new mechanism of regulation of neurotransmitter transport whose malfunction could be involved in abnormal neurotransmitter concentrations and the associated CNS disorders.  In this mechanism, a novel SH2-like domain that appears to be present in most neurotransmitter transporters triggers a rapid inhibition of neurotransmitter transport upon binding to a phosphorylated tyrosine within the same neurotransmitter transporter. Because mutations in this SH2-like domain have been linked to CNS diseases, we hypothesize that drugs that can modulate this regulatory mechanism might enable a new therapeutic approaches to treat these disorders. We are currently developing these drugs.