DEXMETHYLPHENIDATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H19NO2
Molecular Weight	233.3062
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(CCCCN1)[C@H](C(=O)OC)C2=CC=CC=C2

InChI

InChIKey=DUGOZIWVEXMGBE-CHWSQXEVSA-N

InChI=1S/C14H19NO2/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3/t12-,13-/m1/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
[Prescribing ritalin in combined modality management of hyperactivity with attention deficit].	2001 Sep-Oct	11760693
Dexmethylphenidate.	2002	12215063
Dexmethylphenidate (Focalin) for ADHD.	2002 May 13	12011757
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 withdrawal trial of dexmethylphenidate hydrochloride in children with attention deficit hyperactivity disorder.	2004 Winter	15662146
Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder.	2005 Jul	16026226
Efficacy and safety of dexmethylphenidate extended-release capsules in children with attention-deficit/hyperactivity disorder.	2006 Jul	16832318
Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration.	2006 Oct	16999660
The complexity of ADHD: diagnosis and treatment of the adult patient with comorbidities.	2007 Aug	17667893
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
Treatment of adult ADHD: is current knowledge useful to clinicians?	2008 Feb	18728815
Dexmethylphenidate extended release: a review of its use in the treatment of attention-deficit hyperactivity disorder.	2009 Dec	19958043
Focalin XR for ADHD.	2009 Mar 23	19305368
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
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
European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD.	2010 Sep 3	20815868

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

DEXMETHYLPHENIDATE

Official Name

English

Dexmethylphenidate [WHO-DD]

Common Name

English

METHYLPHENIDATE D-THREO-FORM

Common Name

English

2-PIPERIDINEACETIC ACID, .ALPHA.-PHENYL-, METHYL ESTER, (.ALPHA.R,2R)-

Common Name

English

METHYLPHENIDATE D-THREO-FORM [MI]

Common Name

English

dexmethylphenidate [INN]

Common Name

English

DEXMETHYLPHENIDATE [VANDF]

Common Name

English

METHYL (2R)-PHENYL((2R)-PIPERIDIN-2-YL)ACETATE

Systematic Name

English

Classification Tree Code System Code

WHO-VATC

QN06BA11