Grant: Operating Grant

Trace amines (TA) are neurotransmitters involved in many biological functions. Altered levels of TA's have been reported in several disorders including Phenylketonuria, Migraine, Schizophrenia, Hepatic Encephalopathy, Parkinson's Disease (PD) and ADHD. TA's exert their effect by activating a class of receptors termed trace amine associated receptors (TAARs). There are 9 TAAR genes in the human genome. Of hese nine genes, TAAR1 is the best characterized and studies on animals have shown that TAAR1 acts as a negative regulator of dopamine. Dopamine is another very important neurotransmitter which is involved in regulating voluntary movement. In fact, it is mainly the dopamine neurons that degenerate in PD. Considering that TAAR1 acts a negative regulator of dopamine, we hypothesize that TAAR1 antagonists (inhibitors) could have a potential therapeutic benefit for treatment of PD by enhancing the actions of dopamine. The overall goal of this study is to identify new antagonists for TAAR1 that could potentially enhance dopamine transmission and therefore be beneficial for treatment of the motor symptoms in PD. So far, we have identified 4 novel antagonists of TAAR1. Interestingly, our initial studies indicate that one of our antagonists is able to enhance dopamine transmission in rodents and could therefore be a potential beneficial treatment of PD.