LY3154207 is a potent, selective and orally active dopamine D1
receptor positive allosteric modulator (PAM) [1
]. The allosteric binding site of LY3154207 has been determined to reside at the intracellular loop 2 (ICL2) region of the receptor.
PAMs are being developed to address the poor drug-like properties of selective orthosteric D1
agonists. In particular, LY3154207 does not induce tachyphylaxis in preclinical models, whereas orthosteric agonists do. LY3154207 exhibits pro-cognitive and motor-enhancing effects in vivo
, and is being considered for potential utility in the treatment of neuropsychiatric disorders [2