General
Preferred name
METHYLPHENIDATE
Synonyms
METHYLPHENIDATE HYDROCHLORIDE ()
Concerta / Focalin ()
methylphenidate HCl ()
Methylin ()
Oros mph ()
Xenidate XL ()
SPD544 ()
Equasym XL ()
Ritalin La ()
Methylphenidate hydrochloride cii ()
NSC-169868 ()
Quillivant ()
Delmosart ()
Aptensio ()
Aptensio XR ()
Metadate ER ()
Tranquilyn ()
SPD-544 ()
Medikinet XL ()
Ritalin-sr ()
Matoride XL ()
Methylin ER ()
Ritalin ()
Metadate CD ()
Foquest ()
Jornay pm ()
Metadate ()
Quillichew ()
Medikinet ()
Equasym ()
Adhansia xr ()
Quillivant XR ()
Relexxii ()
Ritalin SR ()
Concerta ()
Quillichew ER ()
Methylphenidate extended release ()
Cotempla XR-ODT ()
Daytrana ()
Prc-063 ()
Metilfenidato ()
Threo-dl-methylphenidate ()
P&D ID
PD010035
CAS
298-59-9
113-45-1
Tags
available
drug
Approved by
FDA
First approval
1955
Drug indication
Stimulant (central)
Attention deficit hyperactivity disorder
Traumatic brain injury
Drug Status
approved
investigational
Max Phase
4.0
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS Methylphenidate is a racemic mixture comprised of the d- and l-isomers. The d-isomer is more pharmacologically active than the l-isomer. Radioligand binding studies demonstrate that binding of methylphenidate in the brain is localized to dopamine-rich areas, in particular in the prefrontal cortex which has been demonstrated to play a prominent role in ADHD pathophysiology [A177547]. In a number of animal models, methylphenidate enhances locomotor activity and induces stereotypic behaviours.
DESCRIPTION Methylphenidate is a racemic mixture of optical isomers (enantiomers). We show the chemical structure without specified stereochemistry to represent the mixture. The most active (R,R) enantiomer is the approved drug . Methylphenidate is administered as the hydrochloride salt (PubChem CID 9280). (GtoPdb)
HALF-LIFE Concerta: The half-life of methylphenidate in adults following oral administration of Concerta® was approximately 3.5 h[F4474].; ; Biphentin: Methylphenidate is eliminated from plasma with a mean half-life of 2.4 hours in children and 2.1 hours in adults[F4480].; ; Methylphenidate (immediate release): Methylphenidate is eliminated from the plasma with a mean half-life of 2.4 hours in children and 2.1 hours in adults[F4483].;
MOA While its exact mechanism is unclear, methylphenidate (MPH) has been shown to act as a norepinephrine and dopamine reuptake inhibitor (NDRI), thereby increasing the presence of these neurotransmitters in the extraneuronal space and prolonging their action [A177541]. There is a dose-related effect of psychostimulants on receptor stimulation, where higher doses are shown to increase norepinephrine (NE) and dopamine (DA) efflux throughout the brain which can result in impaired cognition and locomotor-activating effects. In contrast, low doses are found to selectively activate NE and DE neurotransmission within the prefrontal cortex which is an area of the brain thought to play a prominent role in ADHD pathophysiology, thereby improving clinical efficacy and preventing side effects [A177547]. The lower doses used to treat ADHD are not associated with the locomotor-activating effects associated with higher doses and instead reduce movement, impulsivity, and increase cognitive function including sustained attention and working memory [A177541, A177544]. Methylphenidate's beneficial effects in sustaining attention have also been shown to be mediated by alpha-1 adrenergic receptor activity [A177550]. ; ; Clinical findings have shown that children with ADHD have an abnormality in the dopamine transporter gene (DAT1), the D4 receptor gene (DRD-4), and/or the D2 receptor gene that may be at least partly overcome by the dopaminergic effects of methylphenidate, suggesting a possible mode of action [F4474].
ABSORPTION Methylphenidate is readily absorbed in a biphasic manner when orally administered to children diagnosed with ADHD and to healthy adults. The plasma concentration-time profile of methylphenidate demonstrates absorption in two phases with 2 distinct peaks approximately 4 hours apart. In children and adults males, after administration of a single oral dose of Ritalin LA and Ritalin given in two doses 4 hours apart, peak plasma concentration is reached approximately 2 hours for the first phase and 5-6 hours for the second phase. The absolute oral bioavailability of methylphenidate in children was 22±8% for d-methylphenidate and 5±3% for l-methylphenidate. These low values suggest that methylphenidate is highly metabolized pre-systemically.
INDICATION Methylphenidate is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years of age and older and for the treatment of narcolepsy.
MOA Methylphenidate blocks dopamine and norepinephrine reuptake in central adrenergic neurons by blocking dopamine transport or carrier proteins. Methylphenidate acts within the brain stem arousal system and cerebral cortex and causes increased sympathomimetic activity in the central nervous system. Alteration of serotonergic pathways may result due to these changes in dopamine transport.
PHARMACODYNAMICS The mode of therapeutic effect of methylphenidate on the symptoms of ADHD is currently unknown.
Cell lines
1
Organisms
1
Compound Sets
20
ChEMBL Approved Drugs
CHEMBL1722
CHEMBL796
ChEMBL Drugs
CHEMBL1722
CHEMBL796
Concise Guide to Pharmacology 2017/18
7236
Concise Guide to Pharmacology 2019/20
7236
Concise Guide to Pharmacology 2021/22
7236
Concise Guide to Pharmacology 2023/24
7236
DrugBank
DB00422
DrugBank Approved Drugs
DB00422
DrugCentral
1767
DrugCentral Approved Drugs
1767
DrugMAP
DM7SJD6
DrugMAP Approved Drugs
DM7SJD6
DrugMatrix
Guide to Pharmacology
7236
Ki Database
METHYLPHENIDATE
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL1722
CHEMBL796
Natural product-based probes and drugs
NPC Screening Collection
ReFrame library
The Spectrum Collection
External IDs
69
Properties
(calculated by RDKit )
Molecular Weight
233.14
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
1
Rotatable Bonds
3
Ring Count
2
Aromatic Ring Count
1
cLogP
2.09
TPSA
38.33
Fraction CSP3
0.5
Chiral centers
2.0
Largest ring
6.0
QED
0.81
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Therapeutic Indication
ADHD
Therapeutic Class
CNS & PNS
Central Nervous System Stimulants
Source data