SERDEXMETHYLPHENIDATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H29N3O8
Molecular Weight	499.5131
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=UBZPNQRBUOBBLN-PWRODBHTSA-N

InChI=1S/C25H29N3O8/c1-35-24(33)21(17-8-3-2-4-9-17)20-11-5-6-13-28(20)25(34)36-16-27-12-7-10-18(14-27)22(30)26-19(15-29)23(31)32/h2-4,7-10,12,14,19-21,29H,5-6,11,13,15-16H2,1H3,(H-,26,30,31,32)/t19-,20+,21+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021278s008,021802s009lbl.pdf | https://www.drugbank.ca/drugs/DB06701

Dexmethylphenidate is the dextrorotary form of methylphenidate. Dexmethylphenidate is marketed under the trade name Focalin. Focalin (dexmethylphenidate hydrochloride) is the d-threo-enantiomer of racemic methylphenidate hydrochloride, which is a 50/50 mixture of the d-threo and l-threoenantiomers. Focalin is a central nervous system (CNS) stimulant, available in three tablet strengths. Each tablet contains dexmethylphenidate hydrochloride 2.5, 5, or 10 mg for oral administration. Dexmethylphenidate is used as a treatment for ADHD, ideally in conjunction with psychological, educational, behavioral or other forms of treatment. Methylphenidate blocks dopamine uptake in central adrenergic neurons by blocking dopamine transport or carrier proteins. Methylphenidate acts at the brain stem arousal system and the cerebral cortex and causes increased sympathomimetic activity in the central nervous system. Methylphenidate is a catecholamine reuptake inhibitor that indirectly increases catecholaminergic neurotransmission by inhibiting the dopamine transporter (DAT) and norepinephrine transporter (NET), which are responsible for clearing catecholamines from the synapse, particularly in the striatum and meso-limbic system.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine transporter 180 Target ID: CHEMBL238 Sources: https://www.drugbank.ca/drugs/DB06701 \| https://www.ncbi.nlm.nih.gov/pubmed/17218796 \| https://www.ncbi.nlm.nih.gov/pubmed/21129986	Inhibitor 8297		161.0 nM [Ki]
Norepinephrine transporter 191 Target ID: CHEMBL222 Sources: https://www.drugbank.ca/drugs/DB06701 \| https://www.ncbi.nlm.nih.gov/pubmed/17218796 \| https://www.ncbi.nlm.nih.gov/pubmed/17489581	Inhibitor 8297		206.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Attention deficit hyperactivity disorder 68 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021278s008,021802s009lbl.pdf	Primary		Approved 8429	FOCALIN Approved Use Focalin XR is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients aged 6 years and older. The effectiveness of Focalin XR in the treatment of ADHD in patients aged 6 years and older was established in two placebo-controlled studies in patients meeting DSM-IV criteria for ADHD. Launch Date 2001

C_max

Value	Dose	Analyte	Population
23.72 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14747426	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMETHYLPHENIDATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
22.13 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14747426	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMETHYLPHENIDATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
10.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28590363	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMETHYLPHENIDATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
120.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14747426	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMETHYLPHENIDATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
131.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14747426	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMETHYLPHENIDATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
79.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28590363	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMETHYLPHENIDATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
2.68 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14747426	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMETHYLPHENIDATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.81 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14747426	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMETHYLPHENIDATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
3.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28590363	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMETHYLPHENIDATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
40 mg single, oral (min) Overdose Dose: 40 mg Route: oral Route: single Dose: 40 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.11	unhealthy Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.11	Other AEs: Vomiting, Agitation... Other AEs: Vomiting Agitation Tremor Hyperreflexia Muscle twitching Convulsions Euphoria Confusion Hallucinations Delirium Sweating Flushing Headache Hyperpyrexia Tachycardia Palpitations Cardiac arrhythmias Hypertension Mydriasis Mucosal dryness Rhabdomyolysis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.11
30 mg 1 times / day multiple, oral Recommended Dose: 30 mg, 1 times / day Route: oral Route: multiple Dose: 30 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.7	unhealthy Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.7	Disc. AE: Twitching, Anorexia... AEs leading to discontinuation/dose reduction: Twitching (1%) Anorexia (1%) Insomnia (1%) Tachycardia (1%) Insomnia (1.8%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.7
40 mg 1 times / day multiple, oral (max) Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.1	Disc. AE: Cardiac disorders, Stroke... Other AEs: Increased blood pressure, Heart rate increased... AEs leading to discontinuation/dose reduction: Cardiac disorders (grade 3-5) Stroke (grade 3-5) Myocardial infarction (grade 3-5) Seizures Raynaud's phenomenon Other AEs: Increased blood pressure Heart rate increased Psychotic symptom (grade 3-5) Psychotic symptom Manic symptom Aggression Growth suppression Priapism Erection prolonged Vascular disorders Visual disturbance Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.1
40 mg 1 times / day multiple, oral (max) Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.8	unhealthy Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.8	Disc. AE: Feeling jittery, Anorexia... AEs leading to discontinuation/dose reduction: Feeling jittery (1.8%) Anorexia (1.2%) Anxiety (1.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021802s033lbl.pdf Page: p.8

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A 214	esterase 72 CES2 28 P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021278s026lbl.pdf#page=11 Page: 11.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021278s026lbl.pdf#page=11 Page: 11.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021278s026lbl.pdf#page=11 Page: 11.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021278s026lbl.pdf#page=11 Page: 11.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021278s026lbl.pdf#page=11 Page: 11.0	no
CYP3A 298	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021278s026lbl.pdf#page=11 Page: 11.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021278s026lbl.pdf#page=11 Page: 11.0	no	no (co-administration study) Comment: Clinically, methylphenidate coadministration did not increase plasma concentrations of the CYP2D6 substrate desipramine. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021278s026lbl.pdf#page=11 Page: 11.0

Drug as victim

Target	Modality	Activity
CES2 28	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15082749/ Page: -	no
P-gp 1537	substrate 3367 Sources: https://www.pharmgkb.org/pmid/16621932 Page: -	weak
esterase 72	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12215063/ Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:51860	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:51860
ZINC	ZINC000000896711	http://zinc15.docking.org/substances/ZINC000000896711

PubMed

Title	Date	PubMed
The use of a laboratory school protocol to evaluate concepts about efficacy and side effects of new formulations of stimulant medications.	2002	12685522
Dexmethylphenidate--Novartis/Celgene. Focalin, D-MPH, D-methylphenidate hydrochloride, D-methylphenidate, dexmethylphenidate, dexmethylphenidate hydrochloride.	2002	12455205
Neurobehavioral effects of racemic threo-methylphenidate and its D and L enantiomers in rats.	2003 Feb	12543241
D-Methylphenidate is non-genotoxic in in vitro and in vivo assays.	2003 May 9	12742508
A single-dose, two-way crossover, bioequivalence study of dexmethylphenidate HCl with and without food in healthy subjects.	2004 Feb	14747426
A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and d,l-threo-methylphenidate hydrochloride in children with attention-deficit/hyperactivity disorder.	2004 Nov	15502600
Efficacy of two once-daily methylphenidate formulations compared across dose levels at different times of the day: preliminary indications from a secondary analysis of the COMACS study data.	2004 Sep 30	15458569
Open-label study of dexmethylphenidate hydrochloride in children and adolescents with attention deficit hyperactivity disorder.	2004 Winter	15662147
A double-blind, placebo-controlled withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder.	2004 Winter	15662146
Attention deficit/hyperactivity disorder: pharmacotherapy.	2005 Jan	21179640
Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder.	2005 Jul	16026226
Differential effects of amphetamine isomers on dopamine release in the rat striatum and nucleus accumbens core.	2005 Mar	15719230
ADHD in adolescence and adulthood, with a special focus on the dopamine transporter and nicotine.	2006	16640111
Dexmethylphenidate extended release: in attention-deficit hyperactivity disorder.	2006	16620143
Dexmethylphenidate hydrochloride in the treatment of attention deficit hyperactivity disorder.	2006 Dec	19412495
A comparative study on the cost of new antibiotics and drugs of other therapeutic categories.	2006 Dec 20	17183637
[Medical treatments of hyperactive child: about the new pharmaceutical forms of methylphenidate marketed in France].	2006 Jan	16239100
Efficacy and safety of dexmethylphenidate extended-release capsules in children with attention-deficit/hyperactivity disorder.	2006 Jul	16832318
Misuse of "study drugs:" prevalence, consequences, and implications for policy.	2006 Jun 9	16764722
Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration.	2006 Oct	16999660
[Pharmacotherapy of adult Attention Deficit/Hyperactivity Disorder (ADHD): a systematic review].	2007	18167421
The complexity of ADHD: diagnosis and treatment of the adult patient with comorbidities.	2007 Aug	17667893
Similar bioavailability of dexmethylphenidate extended (bimodal) release, dexmethyl-phenidate immediate release and racemic methylphenidate extended (bimodal) release formulations in man.	2007 Dec	18184535
Efficacy and safety of dexmethylphenidate extended-release capsules in adults with attention-deficit/hyperactivity disorder.	2007 Jun 15	17137560
Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate.	2007 May 31	17489581
Impact of attention-deficit/hyperactivity disorder (ADHD) on prescription dug spending for children and adolescents: increasing relevance of health economic evidence.	2007 Nov 15	18005403
The nonmedical use of prescription ADHD medications: results from a national Internet panel.	2007 Oct 31	17974020
A randomized, double-blind, crossover study of once-daily dexmethylphenidate in children with attention-deficit hyperactivity disorder: rapid onset of effect.	2008	18601306
Treatment of adult ADHD: is current knowledge useful to clinicians?	2008 Feb	18728815
Does chirality matter? pharmacodynamics of enantiomers of methylphenidate in patients with attention-deficit/hyperactivity disorder.	2008 Jun	18480679
Evolution of the treatment of attention-deficit/hyperactivity disorder in children: a review.	2008 May	18555941
Attention-deficit/hyperactivity disorder in adults: evidence-based recommendations for management.	2008 Sep	18824823
Management of attention-deficit hyperactivity disorder in adults: focus on methylphenidate hydrochloride.	2009	19721722
Psychopharmacology of ADHD in pediatrics: current advances and issues.	2009	19557112
Once-daily medications for the pharmacological management of ADHD in adults.	2009 Apr	19536322
Efficacy and safety of dexmethylphenidate extended-release capsules administered once daily to children with attention-deficit/hyperactivity disorder.	2009 Aug	19702487
Dexmethylphenidate extended release: a review of its use in the treatment of attention-deficit hyperactivity disorder.	2009 Dec	19958043
Ixabepilone: a new treatment option for the management of taxane-resistant metastatic breast cancer.	2009 Jun 29	21188125
A retrospective claims analysis of combination therapy in the treatment of adult attention-deficit/hyperactivity disorder (ADHD).	2009 Jun 8	19505334
Long-term effectiveness and safety of dexmethylphenidate extended-release capsules in adult ADHD.	2009 Mar	19218542
Focalin XR for ADHD.	2009 Mar 23	19305368
Pharmacotherapy for adult ADHD.	2009 May	19552859
Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial.	2009 Nov	19896571
Dexmethylphenidate for attention deficit hyperactivity disorder.	2009 Nov	19874250
Attention-deficit hyperactivity disorder: recent advances in paediatric pharmacotherapy.	2010	20030423
Real-World Data on: Attention Deficit Hyperactivity Disorder Medication Side Effects.	2010 Apr	20508803
Testing tic suppression: comparing the effects of dexmethylphenidate to no medication in children and adolescents with attention-deficit/hyperactivity disorder and Tourette's disorder.	2010 Aug	20807066
Use of psychostimulants in patients with dementia.	2010 Oct	20736422
European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD.	2010 Sep 3	20815868
Azido-iodo-N-benzyl derivatives of threo-methylphenidate (Ritalin, Concerta): Rational design, synthesis, pharmacological evaluation, and dopamine transporter photoaffinity labeling.	2011 Jan 1	21129986

Patents

Sample Use Guides

In Vivo Use Guide

Focalin (Dexmethylphenidate) is administered twice daily, at least 4 hours apart. Focalin may be administered with or without food. The recommended starting dose of Focalin for patients who are not currently taking racemic methylphenidate, or for patients who are on stimulants other than methylphenidate, is 5 mg/day (2.5 mg twice daily). Dosage may be adjusted in 2.5 to 5 mg increments to a maximum of 20 mg/day (10 mg twice daily). In general, dosage adjustments may proceed at approximately weekly intervals.

Route of Administration: Oral

In Vitro Use Guide

Dexmethylphenidate inhibition [3H]dopamine uptake at human DAT expressed in mouse N2A cells with IC50 156 nM.

Name

Type

Language

SERDEXMETHYLPHENIDATE

Official Name

English

KP-415 INNER SALT

Code

English

serdexmethylphenidate [INN]

Common Name

English

SERDEXMETHYLPHENIDATE [USAN]

Common Name

English

N-(1-((((2R)-2-((1R)-2-METHOXY-2-OXO-1-PHENYLETHYL)PIPERIDINE-1-CARBONYL)OXY)METHYL)PYRIDIN-1-IUM-3-CARBONYL)-L-SERINATE

Systematic Name

English

Serdexmethylphenidate [WHO-DD]

Common Name

English

PYRIDINIUM, 3-((((1S)-1-CARBOXY-2-HYDROXYETHYL)AMINO)CARBONYL)-1-(((((2R)-2-((1R)-2-METHOXY-2-OXO-1-PHENYLETHYL)-1-PIPERIDINYL)CARBONYL)OXY)METHYL)-

Systematic Name

English

Classification Tree Code System Code

DEA NO.

1729