Conformationally Restricted Amines as Regulators of TAAR Activity
T1AM, a metabolite of the thyroid hormone, has previously been shown to be a potent agonist (activator) of the trace amine associated receptor (TAAR). Activation of TAAR in mice yields rapid physiological effects that include a decrease in body temperature, metabolism, and cardiac drive. Regulating the activity of the TAAR could have a profound impact on the lives of those afflicted with thyroid disease. We examined several compounds that share structural similarities to that of T1AM, and could therefore elicit similar TAAR activity. This project dealt specifically with the common drug Apomorphine. We found that R(-)-Apomorphine exhibits dose dependant activation of TAAR (EC50 = 440 nM) however its enantiomer (mirror image) S-(+)-Apomorphine was shown to be an antagonist (inhibitor) for TAAR. Several more amines that represent conformationally restricted or stereospecific analogs of T1AM were also examined.
Faculty Mentor: Matt Hart
Page last modified July 14, 2009