Triple reuptake inhibitors (TRIs) are a relatively new class of antidepressants that impact dopamine, serotonin and norepinephrine neurotransmission. Mayo Clinic researchers, in collaboration with researchers from Virginia Tech, developed a novel TRI (PRC200-SS) with potent transporter binding and efficacy in mouse behavioral models. A large pharmaceutical company licensed this technology and the three organizations collaborated to develop and test improved compounds designed to overcome liabilities observed during preclinical testing. The company has strategically halted development in this area, and the rights to all improved compounds have been returned to Mayo Clinic.
Improved TRI compounds that address liabilities identified during preclinical evaluation. Compounds exhibit a range of binding affinity for the individual transporters, suggesting potential use in indications other than depression. Patent applications are in preparation, indicating a potentially long remaining patent life.
Stage of Development
Evaluation of transporter binding, hERG testing, and CYP2D6 inhibition testing results are available for the improved compounds.
Liang et al. Antidepressant-like pharmacological profile of a novel triple reuptake inhibitor, (1S,2S) - 3 - (methylamino) - 2 - (naphthalene-2-yl) - 1 - phenylpropan-1-ol (PRC200-SS). J Pharmacol Exp Ther 2008; 327(2): 573-83.