Serdexmethylphenidate

Overview

Serdexmethylphenidate (SDX) is a prodrug of dexmethylphenidate created by the pharmaceutical company Zevra Therapeutics. The compound was first approved by the FDA as one of the active ingredients in Azstarys for the treatment of attention deficit hyperactivity disorder (ADHD) in children, adolescents, and adults in March 2021. Serdexmethylphenidate is a prodrug which has a delayed onset of action and a prolonged duration of effects compared to dexmethylphenidate, its parent compound.[1][2] WP

Uses, dosage and effects

Medical uses

The combination serdexmethylphenidate/dexmethylphenidate (Azstarys) was approved by the US Food and Drug Administration (FDA) in March 2021, for the treatment of ADHD in people six years of age and older. Co-formulation of serdexmethylphenidate with dexmethylphenidate allows for a more rapid onset of action while still retaining up to 13 hours of therapeutic efficacy.[1][3][4] WP

Risks and side effects

Abuse potential

The abuse potential of serdexmethylphenidate has been evaluated in clinical studies. Administration of serdexmethylphenidate via common routes of administration used during the abuse of psychostimulants such as insufflation and intravenous injection resulted in significantly reduced systemic exposure to active dexmethylphenidate and thus markedly decreased pharmacodynamic effects when compared to unmodified dexmethylphenidate.[5][6] WP

Following an Eight Factor Analysis by the FDA Controlled Substance Staff (CSS), the U.S. Department of Health and Human Services (HHS) provided a scheduling recommendation to the Drug Enforcement Administration (DEA) to control serdexmethylphenidate and its salts in Schedule IV of the Controlled Substances Act (CSA). Based on this recommendation and its own review, the DEA concluded that serdexmethylphenidate met the criteria for placement in schedule IV of the CSA.[5][7] WP

Pharmacology

Pharmacology

Serdexmethylphenidate has mean terminal plasma elimination half-life of 5.7 hours. Less than 3% of the drug is measurable in circulation intact following oral administration. When administered alone, serdexmethylphenidate produces a dexmethylphenidate tₘₐₓ of 8 hours. It is believed that serdexmethylphenidate is metabolized to dexmethylphenidate primarily in the lower gastrointestinal tract. Enzymes involved in this conversion have yet to be elucidated.[2][8][9] WP

Research

Research

Due to the delayed onset and prolonged duration of effects following oral administration of serdexmethylphenidate, several dosage forms containing serdexmethylphenidate are under investigation for use as long-acting psychostimulant in the treatment of various CNS disorders, substance use disorder (SUD), and sleep disorders. Under the developmental codename KP484, serdexmethylphenidate is being investigated as part of a potential "super-extended duration" psychostimulant, with therapeutic efficacy lasting up to 16 hours following oral administration.[10] WP

In January 2021, the FDA granted approval for clinical trials investigating serdexmethylphenidate (as KP879) for the treatment for stimulant use disorder.[11] WP

Chemistry

Formula

C25H29N3O8 PC

CAS number

1996626-29-9 PC

Molar mass (g/mol)

499.5 PC

IUPAC name (computed by PubChem)

(2S)-3-hydroxy-2-[[1-[[(2R)-2-[(1R)-2-methoxy-2-oxo-1-phenylethyl]piperidine-1-carbonyl]oxymethyl]pyridin-1-ium-3-carbonyl]amino]propanoate PC

SMILES

COC(=O)[C@@H]([C@H]1CCCCN1C(=O)OC[N+]2=CC=CC(=C2)C(=O)N[C@@H](CO)C(=O)[O-])C3=CC=CC=C3 PC

InChIKey

UBZPNQRBUOBBLN-PWRODBHTSA-N PC

PubChem CID

134823895

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Azstarys- serdexmethylphenidate and dexmethylphenidate capsule. 3 November 2022
2. Other KemPharm. KemPharm Announces FDA Approval of Azstarys (serdexmethylphenidate and dexmethylphenidate capsules, for oral use, CII), A New Once-Daily Treatment for ADHD. 3 March 2021
3. Other Mickle T. Prodrugs for ADHD Treatments: Opportunities & Potential to Fill Unmet Medical Needs
4. Journal / agency Bastings E. NDA 212994 Approval. 2 March 2021
5. Other Schedules of Controlled Substances: Placement of Serdexmethylphenidate in Schedule IV. 7 May 2021
6. Journal / agency Braeckman R. Human Abuse Potential of Intravenous Serdexmethylphenidate (SDX), A Novel Prodrug of D-Methylphenidate, in Recreational Stimulant Abusers. Journal of the American Academy of Child & Adolescent Psychiatry. 1 October 2018. doi:10.1016/j.jaac.2018.09.141
7. Other Schedules of Controlled Substances: Placement of Serdexmethylphenidate in Schedule IV. 24 June 2022
8. Journal / agency These highlights do not include all the information needed to use AZSTARYS safely and effectively. See full prescribing information for AZSTARYS. AZSTARYS (serdexmethylphenidate and dexmethylphenidate) capsules, for oral use, CII Initial U.S. Approval: 2021
9. Harm reduction site Serdexmethylphenidate
10. Other Pipeline & Products
11. Other KemPharm Receives FDA Clearance to Initiate KP879 Clinical Program for the Treatment of Stimulant Use Disorder. 27 January 2021

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.