Centanafadine, sold under the brand name Simtriyo, is a medication used for the treatment of attention deficit hyperactivity disorder (ADHD). It is taken orally.
Common side effects of centanafadine include headache, appetite loss, insomnia, nausea, dry mouth, abdominal pain, and rash, among others. It carries a boxed warning for suicidal ideation and behaviors in children and adolescents aged six years and older, as well as for potential abuse, misuse, and addiction. The drug is a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), with preference for norepinephrine and then dopamine over serotonin, and has stimulant effects.
Centanafadine was approved for medical use in the United States in July 2026. Its scheduling as a controlled substance was pending as of August 2026.
Medical uses In the United States, centanafadine is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) in adults and children aged six years and older who weigh at least . Use is not recommended in children younger than six years, as a higher incidence of weight loss was observed, or in those weighing less than , as data is lacking.
Available forms Centanafadine is available in the form of extended-release oral capsules.
Contraindications Contraindications of centanafadine include hypersensitivity to centanafadine or its excipients, concomitant use within 14days of taking or stopping a monoamine oxidase inhibitor (MAOI), and history of pheochromocytoma.
Side effects Side effects of centanafadine include decreased appetite, nausea, rash, abdominal pain, fatigue, insomnia, dry mouth, diarrhea, irritability, elevated mood, and euphoria, among others.
Centanafadine carries a boxed warning for suicidal ideation and behaviors in pediatric patients aged six years and older. In a 6-week placebo-controlled trial in children aged six to twelve years with attention deficit hyperactivity disorder (ADHD), suicide attempt was reported in 0.7% (2 of 304) of participants given centanafadine and in none (0 of 153) of those given placebo. In a long-term open-label study of patients aged six to seventeen years taking centanafadine, suicidal ideation was reported in 0.8% (5 of 620), leading to discontinuation of the medication in 0.6% of participants.
Overdose There is limited experience with overdose of centanafadine. In clinical trials, centanafadine overdose resulted in symptoms including vomiting, tachypnea, tachycardia, and elevated blood pressure. Treatment of centanafadine overdose should be supportive and based on symptoms.
Interactions Centanafadine is primarily metabolized by monoamine oxidase A (MAO-A) and hence should not be taken in combination with monoamine oxidase inhibitors (MAOIs).
Pharmacology Pharmacodynamics Centanafadine is a stimulant and acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI). Its values for monoamine reuptake inhibition have been reported to be 6nM for norepinephrine, 38nM for dopamine, and 83nM for serotonin. Hence, the drug shows 6.3-fold preference for inhibition of norepinephrine reuptake over dopamine reuptake, 13.8-fold preference for inhibition of norepinephrine reuptake over serotonin reuptake, and 2.2-fold preference for inhibition of dopamine reuptake over serotonin reuptake.
+ Activities Site IC50 (nM) Action Ref 83 nM Inhibitor 6 nM Inhibitor 38 nM Inhibitor
Pharmacokinetics Centanafadine is primarily metabolized by monoamine oxidase A (MAO-A). The elimination half-life of centanafadine is 5.2hours.
Chemistry Centanafadine is a substituted naphthylethylamine and cyclized phenethylamine.
Analogues Some structurally related compounds to centanafadine include various compounds containing a naphthyl aromatic ring joined to an aminoalkyl group such as naphthylaminopropane (PAL-287), naphthylmorpholine (PAL-678), methylnaphthidate (HDMP-28), 1-(2-naphthyl)piperazine (2-NP; 1-deazaquipazine) and WF-23, as well as other substituted 3-azabicyclo[3.1.0]hexanes such as bicifadine, amitifadine and DOV-216,303.
History Centanafadine's development began with Euthymics Bioscience after it acquired DOV Pharmaceutical. It was developed as a treatment for attention deficit hyperactivity disorder (ADHD). In 2011, Euthymics Bioscience spun off its development of centanafadine to a new company called Neurovance. In March 2017, Otsuka Pharmaceutical acquired Neurovance and the rights to centanafadine. Centanafadine was approved for medical use in the United States in July 2026.
Society and culture Names Centanafadine is the generic name of the drug and its International Nonproprietary Name (INN) and United States Adopted Name (USAN). It is also known by its former developmental code names EB-1020 and DOV-216419 and is sold under the brand name Simtriyo.
Legal status Centanafadine was approved for medical use in the United States in July 2026. Centanafadine shows misuse liability similar to that of amphetamine in humans. Its controlled substance scheduling is pending in the United States.
Research In addition to its approved indication of attention deficit hyperactivity disorder (ADHD), centanafadine is under development for the treatment of anxiety disorders, major depressive disorder, and smoking withdrawal. As of June 2026, it is in phase 3 clinical trials for anxiety disorders and is in phase 2 trials for major depressive disorder and smoking withdrawal. The drug was also under development for the treatment of binge eating disorder and neuropathic pain, but development for these indications was discontinued.
A June 2026 a randomised double blind and placebo controlled clinical trial design to evaluate the efficacy and safety of centanafadine. Found it to be most effective in adolescent (13-17) use cases where the non stimulant affect of the drug made it better for adolescents experiencing change in physicality and autonomy at a pubescent age, where the likelihood of stimulant abuse increases. The trial suggested that doses of 328.8 mg to be the most effective at treating symptoms of ADHD in adolescent that reducing their ADHD-RS-5 scale rating score over 6 weeks.
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