文摘
Herein, we report the structure鈥揳ctivity relationship of a chiral morpholine-based scaffold, which led to the identification of a potent and selective dopamine 4 (D4) receptor antagonist. The 4-chlorobenzyl moiety was identified, and the compound was designated an MLPCN probe molecule, ML398. ML398 is potent against the D4 receptor with IC50 = 130 nM and Ki = 36 nM and shows no activity against the other dopamine receptors tested (>20 渭M against D1, D2S, D2L, D3, and D5). Further in vivo studies showed that ML398 reversed cocaine-induced hyperlocomotion at 10 mg/kg.
Keywords:
Dopamine 4 receptor antagonist; ML398; addiction; MLPCN