Centanafadine (Simtriyo): a triple monoamine reuptake inhibitor for ADHD.

Centanafadine (EB-1020, CTN), also known as (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane, is a norepinephrine-preferring triple (norepinephrine–dopamine–serotonin) reuptake inhibitor. The free base has a molecular formula C15H15N and a molecular weight of 209.3 g/mol; the drug is formulated as the hydrochloride salt (C15H15N·HCl, 245.7 g/mol). The molecule consists of a 3-azabicyclo[3.1.0]hexane core bearing a naphthalen-2-yl group at position 1, with (1R,5S) stereochemistry. Centanafadine is highly bound to plasma proteins, with an unbound fraction of less than 0.01, and it distributes extensively into extravascular tissues. The compound has a mean elimination half-life of 5.2 h and readily crosses the blood–brain barrier. Centanafadine is metabolized primarily by monoamine oxidase A to a lactam metabolite that lacks pharmacological activity. Clearance occurs predominantly through metabolism followed by renal excretion, with a minor contribution from fecal elimination.