Centanafadine Pharmacological Profile Affirms Potential for Treatment of ADHD

Centanafadine shows potential benefit to treat symptoms of attention deficit hyperactive disorder (ADHD), according to poster data presented at the American Professional Society of ADHD and Related Diseases, in San Diego, California, January 15-18, 2026.¹ The drug was confirmed as a norepinephrine, dopamine, serotonin reuptake inhibitor (NDSRI), and showed unique activity across all monoamine transporters.

The study utilized intracerebral microdialysis on rats to measure the effects of centanafadine on extracellular monoamines in the prefrontal cortex and ventral striatum. Action in these regions is considered critical in ADHD treatment. Locomotor activity and microdialysis were performed at the same time, according to the Culex Bambino/Raturn system. After baseline sampling at 80 minutes, centanafadine 3, 10, or 30 mg/kg or vehicle was administered to the test and vehicle rat groups. Dialysate samples were collected at 20-minute intervals for 4 hours after administration. Monoamine concentration was quantified by high-performance liquid chromatography with electrochemical detection.

Data showed potential for benefit in symptoms associated with ADHD, such as emotional dysregulation, executive function deficits, and comorbid anxiety symptoms. Centanafadine increased extracellular concentrations of norepinephrine, dopamine, and serotonin in cortical and subcortical regions, dependent on dose. Increases in concentration plateaued around 60 minutes, with effects maintained through 4 hours. The drug had no effect on locomotor activity compared with vehicle, indicating a low risk for unwanted psychomotor activity. Increases of monoamines in the prefrontal cortex included average increases (over 0-4 hours) of 1184% for serotonin, 604% for norepinephrine, and 281% for dopamine, all with P < 0.001). The effect of centanafadine on serotonin was also greater than previously predicted based on in vitro observations. Peak increases in serotonin in vivo were 1638% and 1184% in the prefrontal cortex and 1590% and 1119% in the ventral striatum (at 30mg/kg dose (P < 0.001)) at 80 minutes and 0-4 hour average, respectively.

Centanafadine is an NDSRI currently under investigation for treatment of ADHD. In previous phase 3 trials, it has shown positive efficacy and safety results in children, adolescents, and adults. A randomized controlled trial of centanafadine in adolescents showed a 328.8 mg dose was efficacious for treatment of ADHD in ages 13 to 17.² A 52-week open-label safety and tolerability showed centanafadine sustained release 400 mg was safe and efficacious for long-term treatment of adults with ADHD.³ Otsuka Pharmaceuticals, the developer of centanafadine, submitted a New Drug Application with the US Food and Drug Administration in November of 2025.⁴

References

1. Heal DJ, Smith SL, Gosden J, et al. Pharmacological characterization of centanafadine—potential implications for efficacy and safety in ADHD and comorbid psychiatric disorders. Poster presented at: American Professional Society of ADHD and Related Diseases; January 15-18, 2025; San Diego, California. Accessed January 15, 2026.

2. Ward CL, Childress AC, Jin N, et al. Centanafadine for attention-deficit/hyperactivity disorder in adolescents: a randomized clinical trial. J Am Acad Child Adolesc Psychiatry. Published online July 4, 2025.

3. Mattingly GW, Turkoglu O, Chang D, et al. 52-week open-label safety and tolerability study of centanafadine sustained release in adults with attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2025;45(5):454-462.

4. Otsuka Pharmaceuticals submits new drug application to US FDA for centanafadine for the treatment of ADHD in children, adolescents, and adults. Press release. November 24, 2025. Accessed January 15, 2026. https://www.otsuka-us.com/news/otsuka-pharmaceutical-submits-new-drug-application-us-fda-centanafadine-treatment-adhd