FMF-01-042

FMF-01-042 (also known as FMJ-01-042) is a blood-brain barrier-permeable, low-efficacy partial agonist of the dopamine D4 receptor (D4R) with high affinity (Ki = 4.33 nM) and exceptional subtype selectivity (≥ 1510-fold versus D2R and ≥ 2504-fold versus D3R). Developed by researchers at High Point University and Rowan University, FMF-01-042 was designed using click chemistry to bioisosterically replace the metabolically unstable amide linker of previous D4R ligands with a 1,2,3-triazole moiety. This modification significantly improves metabolic stability in liver microsomes and enhances in vivo pharmacokinetics, showing excellent brain penetration in rat models. FMF-01-042 is being investigated as a pharmacological tool and potential therapeutic candidate for neuropsychiatric disorders, including substance use disorders (such as cocaine use disorder) and attention-deficit/hyperactivity disorder (ADHD).