METHYLPHENIDATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C14H19NO2
Molecular Weight	233.3062
Optical Activity	( + / - )
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-STQMWFEESA-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-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/010187s087lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/25120227

Methylphenidate is a CNS stimulant approved for the treatment of narcolepsy and attention deficit hyperactivity disorder. The drug is believed to bind the dopamine transporter in the presynaptic cell membrane, thereby blocking the reuptake of dopamine and causing an increase in extracellular dopamine levels.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium-dependent dopamine transporter 42 Target ID: Q01959 Gene ID: 6531.0 Gene Symbol: SLC6A3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25120227	Blocker 537

Conditions

Condition	Modality	Targets	Highest Phase	Product
Attention deficit hyperactivity disorder 68 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/010187s087lbl.pdf	Primary		Approved 8429	RITALIN Approved Use Ritalin is indicated for the treatment of Attention Deficit Disorders and Narcolepsy. Launch Date 1955
Narcolepsy 20 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/010187s087lbl.pdf	Primary		Approved 8429	RITALIN Approved Use Ritalin is indicated for the treatment of Attention Deficit Disorders and Narcolepsy. Launch Date 1955

C_max

Value	Dose	Co-administered	Analyte	Population
3.7 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021121s038lbl.pdf	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:		METHYLPHENIDATE HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
41.8 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021121s038lbl.pdf	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:		METHYLPHENIDATE HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021121s038lbl.pdf	18 mg single, oral dose: 18 mg route of administration: Oral experiment type: SINGLE co-administered:		METHYLPHENIDATE HYDROCHLORIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
90% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/010187s091,018029s059lbl.pdf	unknown, unknown		METHYLPHENIDATE HYDROCHLORIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
700 mg multiple, oral Studied dose Dose: 700 mg Route: oral Route: multiple Dose: 700 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12444349/ https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/010187s091,018029s059lbl.pdf	unhealthy, 45 years n = 1 Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorders Age Group: 45 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/12444349/ https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/010187s091,018029s059lbl.pdf	Other AEs: Abuse... Other AEs: Abuse Sources: https://pubmed.ncbi.nlm.nih.gov/12444349/ https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/010187s091,018029s059lbl.pdf
210 mg 1 times / day single, oral Studied dose Dose: 210 mg, 1 times / day Route: oral Route: single Dose: 210 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20158630/	unhealthy, 8 years n = 1 Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorders Age Group: 8 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20158630/	Other AEs: Hypertension, Tachycardia... Other AEs: Hypertension (grade 1) Tachycardia (grade 1) Confusion Irritability Agitation Hallucinations Sources: https://pubmed.ncbi.nlm.nih.gov/20158630/
15 mg 2 times / day single, oral (mean) Recommended Dose: 15 mg, 2 times / day Route: oral Route: single Dose: 15 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-284_Ritalin%20LA_medr.pdf Page: nda/2002/21-284_Ritalin%20LA_medr.pdf - p.15	healthy, mean age 30 years n = 61 Health Status: healthy Age Group: mean age 30 years Sex: M+F Population Size: 61 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-284_Ritalin%20LA_medr.pdf Page: nda/2002/21-284_Ritalin%20LA_medr.pdf - p.15	Disc. AE: Headache, Nausea... AEs leading to discontinuation/dose reduction: Headache (1.6%) Nausea (1.6%) Hot flushes (1.6%) Panic attack (1.6%) Nausea (1.6%) Vomiting (1.6%) Dizziness (1.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-284_Ritalin%20LA_medr.pdf Page: nda/2002/21-284_Ritalin%20LA_medr.pdf - p.15
12.5 mg 2 times / day multiple, oral (mean) Recommended Dose: 12.5 mg, 2 times / day Route: oral Route: multiple Dose: 12.5 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-284_Ritalin%20LA_medr.pdf Page: nda/2002/21-284_Ritalin%20LA_medr.pdf - p.15	unhealthy, median age 9 years n = 65 Health Status: unhealthy Condition: Attention Deficit Hyperactivity Disorders Age Group: median age 9 years Sex: M+F Population Size: 65 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-284_Ritalin%20LA_medr.pdf Page: nda/2002/21-284_Ritalin%20LA_medr.pdf - p.15	Disc. AE: Fatigue, Lethargy... AEs leading to discontinuation/dose reduction: Fatigue (1.5%) Lethargy (1.5%) Hypomania (1.5%) Anger (1.5%) Anxiety (1.5%) Migraine (1.5%) Depression (1.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-284_Ritalin%20LA_medr.pdf Page: nda/2002/21-284_Ritalin%20LA_medr.pdf - p.15

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A 214	CYP450 65

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021284s020lbl.pdf#page=10 Page: 10.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021284s020lbl.pdf#page=10 Page: 10.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021284s020lbl.pdf#page=10 Page: 10.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021284s020lbl.pdf#page=10 Page: 10.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021284s020lbl.pdf#page=10 Page: 10.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021284s020lbl.pdf#page=10 Page: 10.0	no
CYP3A 298	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021284s020lbl.pdf#page=10 Page: 10.0	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP450 65	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021284s020lbl.pdf#page=10 Page: 10.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/19281853/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY439381
ACT Chemical	ACT11949
Cayman Chemical	11639
Compound Cloud	4158
Compound Cloud	9280
Frontier Scientific Services	500043407
Hairui	HR149584
Hairui	HR149758
Hangzhou Yuhao Chemical Technology	YH52696
HongKong Chemhere	SCD01790
HongKong Chemhere	SCD01793
Innovapharm	BBV-00092182
Lab Seeker	SC-83308
Molcore	MC439381
MuseChem	M071965
MuseChem	M125947
Princeton BioMolecular Research	PBMR221641
ShangHai Biochempartner	BCP18286
Sigma Aldrich	M-083
Sigma Aldrich	M-083\|CERILLIAN
Sigma Aldrich	M2892
Sigma Aldrich	M6935\|SIGMA
Sigma Aldrich	Y0001017\|SIAL
Tetrahedron	TS00164
Tocris	1812
Toronto Research Chemicals	KIT2500
Toronto Research Chemicals	M325671
Toronto Research Chemicals	M325680
ZINC	ZINC000002522648	http://zinc15.docking.org/substances/ZINC000002522648
mcule	MCULE-3118022991
mcule	MCULE-3797509037
mcule	MCULE-5458926987

PubMed

Title	Date	PubMed
Letter: Methylphenidate reaction.	1975 Jun	1134893
Synthesis and pharmacology of site specific cocaine abuse treatment agents: a new synthetic methodology for methylphenidate analogs based on the Blaise reaction.	2001 Apr	11461755
Toward individualized evidence-based medicine: five "N of 1" trials of methylphenidate in geriatric patients.	2001 Apr	11347795
Pharmacotherapeutic management of autism.	2001 Apr	11336609
Present and future pharmacotherapeutic options for adult attention deficit/hyperactivity disorder.	2001 Apr	11336608
An adolescent who abruptly stops his medication for attention-deficit hyperactivity disorder.	2001 Apr	11332803
The influence of a token economy and methylphenidate on attentive and disruptive behavior during sports with ADHD-diagnosed children.	2001 Apr	11317639
Understanding Rx options for the youngest patients.	2001 Aug	11496582
Concerns about Ritalin.	2001 Aug	11487772
Rewarding properties of methylphenidate: sensitization by prior exposure to the drug and effects of dopamine D1- and D2-receptor antagonists.	2001 Aug	11454915
[Methylphenidate therapy in 141 patients with hyperkinetic disorder or with pervasive developmental disorder and hyperkinesia].	2001 Jul	11494575
A comparison of the visual symptoms between ADD/ADHD and normal children.	2001 Jul	11486939
Stimulant drugs for severe hyperactivity in childhood.	2001 Jul	11471516
Rehabilitative management of post-stroke visuospatial inattention.	2001 Jul 10	11400902
Methylphenidate increases the motor effects of L-Dopa in Parkinson's disease: a pilot study.	2001 Jul-Aug	11479391
Correlations between motor persistence and plasma levels in methylphenidate-treated boys with ADHD.	2001 Jun	11466170
Advances in paediatric neuropsychopharmacology: an overview.	2001 Jun	11466164
Adult ADHD. Controlled medication assessment.	2001 Jun	11462747
Effect of repeated methylphenidate administration on presynaptic dopamine and behaviour in young adult rats.	2001 Jun	11448090
Comparison in symptoms between aged and younger patients with narcolepsy.	2001 Jun	11422857
The development of selective attention in children with attention deficit hyperactivity disorder.	2001 Jun	11411785
Attention deficit hyperactivity disorder and substance use disorders: Is there a causal link?	2001 Jun	11399213
Effects of TENS and methylphenidate in tuberculous meningo-encephalitis.	2001 Jun	11394974
Explosive outbursts associated with methylphenidate.	2001 Jun	11392335
Managing stimulant medication for attention-deficit/hyperactivity disorder.	2001 Jun	11389305
Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings.	2001 Jun	11389303
Reinforcing and subject-rated effects of methylphenidate and d-amphetamine in non-drug-abusing humans.	2001 Jun	11386490
Practice parameters for the treatment of narcolepsy: an update for 2000.	2001 Jun 15	11403530
Commentary on Greene and Ablon: What does the MTA study tell us about effective psychosocial treatment for ADHD?	2001 Mar	11482297
Assessing the abuse potential of methylphenidate in nonhuman and human subjects: a review.	2001 Mar	11325419
alpha(2C)-Adrenoceptors modulate the effect of methylphenidate on response rate and discrimination accuracy in an operant test.	2001 Mar 15	11397547
[Prescription of central nervous system stimulants].	2001 Mar 20	11332376
[Neuropsychological follow-up of attention deficit/hyperactive disorder in adulthood before and after treatment with methylphenidate].	2001 May	11428307
Short-term cardiovascular effects of methylphenidate and adderall.	2001 May	11349696
Psychostimulants in preschool children with attention-deficit/hyperactivity disorder: clinical evidence from a developmental disorders institution.	2001 May	11349695
An auditable protocol for treating attention deficit/hyperactivity disorder.	2001 May	11316683
Methylphenidate sensitization is modulated by valproate.	2001 May 25	11411804
[Is Ritalin prescribed insufficiently to hyperactive children in Nordland?].	2001 May 30	11446022
Methylphenidate for fatigue in advanced cancer: a prospective open-label pilot study.	2001 May-Jun	11406895
Gilles de la Tourette Syndrome.	2001 May-Jun	11391121
Emergence of tics in children with attention deficit hyperactivity disorder treated with stimulant medications.	2001 May-Jun	11349243
Methylphenidate improves HIV-1-associated cognitive slowing.	2001 Spring	11449032
Methylphenidate in stimulants abuse: three case reports.	2001 Spring	11444161
Retrospective comparison of Adderall and methylphenidate in the treatment of attention deficit hyperactivity disorder.	2001 Spring	11322743
Early methylphenidate administration to young rats causes a persistent reduction in the density of striatal dopamine transporters.	2001 Spring	11322741
Can methylphenidate facilitate sleep in children with attention deficit hyperactivity disorder?	2001 Spring	11322740
Methylphenidate augmentation of citalopram in elderly depressed patients.	2001 Summer	11481139
Myoclonus during prolonged treatment with sertraline in an adolescent patient.	2001 Summer	11436961
Pharmacokinetic interactions between cyclosporine and bupropion or methylphenidate.	2001 Summer	11436960
Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a reanalysis using drug-placebo and drug-drug response curve methodology.	2001 Summer	11436957

Patents

Sample Use Guides

In Vivo Use Guide

Administer in divided doses 2 or 3 times daily, preferably 30 to 45 minutes before meals. Average dosage is 20 to 30 mg daily. Some patients may require 40 to 60 mg daily. In children the starting dose is 5 mg twice daily (before breakfast and lunch) with gradual increments of 5 to 10 mg weekly.

Route of Administration: Oral

In Vitro Use Guide

Murine neural stem cells were treated directly after seeding to the cover-slip using different concentration (0 nM, 1 nM, 10 nM, 100 nM) of methylphenidate. The drug was found to enhance neuronal differentiation and inhibit neural proliferation.

Name

Type

Language

METHYLPHENIDATE

Official Name

English

METHYLPHENIDATE [VANDF]

Common Name

English

α-Phenyl-2-piperidineacetic acid methyl ester

Systematic Name

English

METHYLPHENIDATE [ORANGE BOOK]

Common Name

English

methylphenidate [INN]

Common Name

English

METHYLPHENIDATE EXTENDED RELEASE

Common Name

English

2-PIPERIDINEACETIC ACID, .ALPHA.-PHENYL-, METHYL ESTER

Common Name

English

METHYLPHENIDATE [HSDB]

Common Name

English

PRC-063

Common Name

English

THREO-DL-METHYLPHENIDATE

Common Name

English

COTEMPLA XR-ODT

Brand Name

English

Methylphenidate [WHO-DD]

Common Name

English

DAYTRANA

Brand Name

English

METHYLPHENIDATE [MI]

Common Name

English

METHYLPHENIDATE [MART.]

Common Name

English

METHYLPHENIDATE [II]

Common Name

English

METHYLPHENIDATE [USAN]

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK547941