Centanafadine

Centanafadine
Molecular structure of centanafadine
3D representation of a centanafadine molecule
Clinical data
Pronunciationsen-tan-af-a-deen[1]
Trade namesSimtriyo
Other namesCTN; EB-1020; EB1020; EB-1020-SR; DOV-216,419; DOV-216419; DOV216419
AHFS/Drugs.comSimtriyo
License data
Routes of
administration		Oral[2]
Drug classSerotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI); Stimulant
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Protein binding>99%[2]
MetabolismMonoamine oxidase A (MAO-A)[2]
Elimination half-life5.2 hours[2]
ExcretionUrine: 88%[2]
Feces: 7%[2]
Identifiers
  • (1R,5S)-1-naphthalen-2-yl-3-azabicyclo[3.1.0]hexane
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC15H15N
Molar mass209.292 g·mol−1
3D model (JSmol)
  • C1[C@H]2[C@@]1(CNC2)C3=CC4=CC=CC=C4C=C3
  • InChI=1S/C15H15N/c1-2-4-12-7-13(6-5-11(12)3-1)15-8-14(15)9-16-10-15/h1-7,14,16H,8-10H2/t14-,15+/m1/s1
  • Key:HKHCSWPSUSWGLI-CABCVRRESA-N

Centanafadine, sold under the brand name Simtriyo, is a medication used for the treatment of attention deficit hyperactivity disorder (ADHD).[2] It is taken by mouth.[2]

Common side effects of centanafadine include headache, appetite loss, insomnia, nausea, dry mouth, abdominal pain, and rash, among others.[2] 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.[2] The drug is a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), with preference for norepinephrine and then dopamine over serotonin, and has stimulant effects.[3][2]

Centanafadine was approved for medical use in the United States in July 2026.[2][4] Its scheduling as a controlled substance was pending as of August 2026.[2][4]

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 20 kg (44 lb).[2] 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 20 kg (44 lb), as data is lacking.[2]

Available forms

Centanafadine is available in the form of extended-release oral capsules.[2]

Contraindications

Contraindications of centanafadine include hypersensitivity to centanafadine or its excipients, concomitant use within 14 days of taking or stopping a monoamine oxidase inhibitor (MAOI), and history of pheochromocytoma.[2]

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.[2]

Centanafadine carries a boxed warning for suicidal ideation and behaviors in pediatric patients aged six years and older.[2] 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.[2]

Overdose

There is limited experience with overdose of centanafadine.[2] In clinical trials, centanafadine overdose resulted in symptoms including vomiting, tachypnea, tachycardia, and elevated blood pressure.[2] Treatment of centanafadine overdose should be supportive and based on symptoms.[2]

Interactions

Centanafadine is primarily metabolized by monoamine oxidase A (MAO-A) and hence should not be taken in combination with monoamine oxidase inhibitors (MAOIs).[2]

Pharmacology

Pharmacodynamics

Centanafadine is a stimulant and acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI).[2][5] Its IC50Tooltip half-maximal inhibitory concentration values for monoamine reuptake inhibition have been reported to be 6 nM for norepinephrine, 38 nM for dopamine, and 83 nM for serotonin.[5] 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.[5]

Activities[5]
SiteIC50 (nM)ActionRef
SERTTooltip Serotonin transporter83 nMInhibitor[5]
NETTooltip Norepinephrine transporter6 nMInhibitor[5]
DATTooltip Dopamine transporter38 nMInhibitor[5]

Pharmacokinetics

Centanafadine is primarily metabolized by monoamine oxidase A (MAO-A).[2] The elimination half-life of centanafadine is 5.2 hours.[2]

Chemistry

Centanafadine is a substituted naphthylethylamine and cyclized phenethylamine.[6]

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.[3] It was developed as a treatment for attention deficit hyperactivity disorder (ADHD).[3][7] In 2011, Euthymics Bioscience spun off its development of centanafadine to a new company called Neurovance.[8] In March 2017, Otsuka Pharmaceutical acquired Neurovance and the rights to centanafadine.[9] Centanafadine was approved for medical use in the United States in July 2026.[4]

Society and culture

Names

Centanafadine is the generic name of the drug and its International Nonproprietary Name (INN)[10] and United States Adopted Name (USAN).[6] It is also known by its former developmental code names EB-1020 and DOV-216419[3] and is sold under the brand name Simtriyo.[2]

Centanafadine was approved for medical use in the United States in July 2026.[2] Centanafadine shows misuse liability similar to that of amphetamine in humans.[2] Its controlled substance scheduling is pending in the United States.[2]

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.[3] 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.[3] The drug was also under development for the treatment of binge eating disorder and neuropathic pain, but development for these indications was discontinued.[3]

References

  1. ↑ "Statement on a Nonproprietary Name Adopted by the USAN Council: Centanafadine" (PDF). United States Adopted Names Council, American Medical Association. 28 May 2014. Archived (PDF) from the original on 10 August 2026. Retrieved 10 August 2026.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 "SIMTRIYO® (centanafadine) extended-release capsules: US prescribing information" (PDF). US Food and Drug Administration/Otsuka America Pharmaceutical, Inc. July 2026. Archived (PDF) from the original on 10 August 2026. Retrieved 10 August 2026.
  3. 1 2 3 4 5 6 7 "Centanafadine - Otsuka Pharmaceutical". AdisInsight. 30 June 2026. Retrieved 28 July 2026.
  4. 1 2 3 "Otsuka Receives FDA Approval for First-in-Class Simtriyo (centanafadine) for the Treatment of Attention-Deficit Hyperactivity Disorder (ADHD) in Adults and Pediatric Patients Aged 6 Years and Older" (Press release). Otsuka. 24 July 2026. Archived from the original on 4 August 2026. Retrieved 25 July 2026.
  5. 1 2 3 4 5 6 7 Bymaster FP, Golembiowska K, Kowalska M, Choi YK, Tarazi FI (June 2012). "Pharmacological characterization of the norepinephrine and dopamine reuptake inhibitor EB-1020: implications for treatment of attention-deficit hyperactivity disorder". Synapse. 66 (6): 522–532. doi:10.1002/syn.21538. PMID 22298359. S2CID 38850652.
  6. 1 2 "Centanafadine". PubChem. Retrieved 28 July 2026.
  7. ↑ "A Matching-Adjusted Indirect Comparison (MAIC) of Centanafadine versus Methylphenidate Hydrochloride in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD): Short-Term Safety and Efficacy Outcomes: Comparaison indirecte ajustée par appariement (MAIC) entre centanafadine et le chlorhydrate de méthylphénidate chez les adultes atteints d'un trouble déficitaire de l'attention avec ou sans hyperactivité (TDAH) : Résultats en matière d'innocuité et d'efficacité à court terme". www.analysisgroup.com. Retrieved 6 August 2026.
  8. ↑ "Euthymics Bioscience, Inc. Presents Data That Support Advancing EB-1020 into Clinical Trials for Adult ADHD". Fierce Pharma. 7 December 2011. Archived from the original on 31 July 2026. Retrieved 31 July 2026.
  9. ↑ "Otsuka Pharmaceutical to Acquire Neurovance, Inc" (Press release). Otsuka. 1 March 2017. Archived from the original on 10 August 2026. Retrieved 10 August 2018.
  10. ↑ World Health Organization (2015). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 74". WHO Drug Information. 29 (3). hdl:10665/331070.
  • Clinical trial number NCT05428033 for "A Trial of Centanafadine Efficacy and Safety in Children With Attention-deficit/Hyperactivity Disorder (ADHD)" at ClinicalTrials.gov
  • Clinical trial number NCT05257265 for "A Trial of Centanafadine Efficacy and Safety in Adolescents With Attention- Deficit/Hyperactivity Disorder" at ClinicalTrials.gov
  • Clinical trial number NCT03605680 for "A Trial Evaluating the Efficacy, Safety, & Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder" at ClinicalTrials.gov
  • Clinical trial number NCT03605836 for "A Trial to Evaluate the Efficacy, Safety, and Tolerability of Centanafadine Sustained-release Tablets in Adults With Attention-deficit/Hyperactivity Disorder" at ClinicalTrials.gov
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