Methylphenidate

methyl 2-phenyl-2-(piperidin-2-yl)acetate

Overview

Methylphenidate belongs to Stimulants.

Key safety note: Methylphenidate is a first-line ADHD medicine with well-established efficacy and a generally favourable safety profile when prescribed and monitored, but it is a Schedule II/controlled stimulant with real risks.^[6]^[7]

Effects

Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.

Therapeutic effects: improved sustained attention and concentration, reduced hyperactivity and impulsivity, and increased wakefulness. At recreational doses, stimulation, increased energy and motivation, and mild euphoria.
Sympathetic/physical effects: raised heart rate and blood pressure, reduced appetite, dry mouth, dilated pupils and, at higher doses, teeth grinding and restlessness.
Comedown/offset: rebound fatigue, low mood, irritability, difficulty concentrating and insomnia: often more pronounced after non-medical binge dosing.

Dosing & duration

Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral (immediate-release tablets or long-acting/extended-release formulations). The figures below are therapeutic (prescribing) ranges, not a recreational recommendation.. Methylphenidate is a prescription medicine. Therapeutic dosing is individualised and titrated by a clinician. The ranges below are typical oral ADHD doses of the RACEMATE (Ritalin/Concerta/Medikinet), not a recreational guide. The isolated active enantiomer dexmethylphenidate (Focalin) is dosed at roughly HALF these milligrams: immediate-release 2.5 mg twice daily up to ~20 mg/day, extended-release 5–10 mg once daily up to ~30 mg/day (ages 6–17) or ~40 mg/day (adults). Non-medical use, crushing tablets to insufflate or inject, is dangerous: the insoluble fillers damage the nasal lining and, if injected, the lungs ('Ritalin lung'), and fast, high dosing drives compulsive redosing, cardiovascular strain and a harsh comedown. Never combine with MAOIs or other stimulants.

Dose ranges

Starting (IR)

5 mg once–twice daily (children ≥6 y), titrated

Typical (IR)

20–30 mg/day in divided doses

Max (IR)

≈60 mg/day

Extended-release

18 mg once daily, up to ~54 mg/day (children) or ~72 mg/day (adolescents/adults)

Duration

onset

Immediate-release ≈20–60 min

total

Immediate-release ≈3–4 h, extended-release ≈8–12 h

after effects

Possible rebound: fatigue, low mood, irritability, poor concentration

Chemical & Physical Properties

Formula	C14H19NO2
Molar mass	233.31 g/mol
State	Solid (crystalline)
Melting point	>200 °C (hydrochloride salt, the medicinal form, the free base melts far lower)
Boiling point	135–137 °C at 0.6 mmHg (free base)
Density	Not reported
Vapor pressure	Not reported
pKa	8.9 (basic amine)
LogP	2.1 (octanol–water, neutral form), ≈0.2 as logD at pH 7.2, where the basic amine is mostly ionised
Solubility	Free base: practically insoluble in water (~1.3 g/L). Soluble in alcohol, ethyl acetate and ether, Hydrochloride salt (Ritalin/Concerta): freely water-soluble: the reason the medicine is formulated as the salt
Refractive index	Not reported

Identifiers & Synonyms

CAS	113-45-1
CAS (enantiomer)
PubChem CID	4158
InChIKey	DUGOZIWVEXMGBE-UHFFFAOYSA-N
InChI	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
SMILES	COC(=O)C(C1CCCCN1)C2=CC=CC=C2

Synonyms

Ritalin
Concerta
Medikinet
MPH
Dexmethylphenidate
Focalin
Focalin XR
d,l-threo-methylphenidate
d-threo-methylphenidate

Pharmacodynamics & Biochemistry

Methylphenidate (Ritalin, Concerta, Medikinet) is a norepinephrine–dopamine reuptake inhibitor (NDRI): it blocks the dopamine (DAT) and noradrenaline (NET) transporters, raising synaptic dopamine and noradrenaline, particularly in the prefrontal cortex and striatum, which underlies its therapeutic effects on attention, impulse control and wakefulness in ADHD and narcolepsy. Crucially, and unlike amphetamine, it is a reuptake blocker rather than a releaser: it does not act as a transporter substrate to pump neurotransmitter out of the nerve terminal. It has negligible affinity for the serotonin transporter (SERT), so it lacks the serotonergic/entactogenic character of amphetamine-type releasers. The marketed drug is racemic threo-methylphenidate: a 1:1 mixture of the d-threo (R,R) and l-threo (S,S) enantiomers (of the two possible diastereomers, only the threo pair is used, the erythro isomers are not). Almost all of the activity resides in the d-threo enantiomer, which is also marketed on its own as the single-isomer medicine dexmethylphenidate (Focalin, d-threo, CAS 40431-64-9, PubChem CID 154101). The l-threo enantiomer is largely inactive and is rapidly cleared by first-pass hydrolysis, so purified d-threo is roughly twice as potent milligram-for-milligram as the racemate. In human transporter assays methylphenidate inhibits catecholamine uptake in the tens-to-low-hundreds-of-nanomolar range (GtoPdb: NET IC50 ≈ 63 nM, DAT IC50 ≈ 79 nM for the racemate), with essentially no serotonin-transporter activity. The isolated active d-threo enantiomer (dexmethylphenidate) binds the human dopamine transporter with Ki ≈ 25 nM and has weaker activity at NET, and a weak in-vitro 5-HT1A partial agonism has been reported but is of uncertain relevance. Its therapeutic, reinforcing and stimulant effects all follow from this catecholamine-reuptake blockade. The reinforcing/abuse potential tracks the speed and degree to which it raises striatal dopamine, which is why route and formulation (fast oral/insufflated/IV vs slow extended-release) strongly shape its liability.

Biological targets

Binding & functional measurements

Target	Measurement	Species
Dopamine transporter	Ki 60 ± 10 nM	Human
Dopamine transporter	Ki 260 ± 30 nM	Mouse
Noradrenaline transporter	Ki 100 ± 10 nM	Human
Noradrenaline transporter	Ki 170 ± 30 nM	Mouse

Pharmacokinetics

Bioavailability	Oral ≈11–52% (extensive, variable first-pass metabolism)
T_max	Immediate-release ≈1–2 h (dexmethylphenidate ≈1–1.5 h), extended-release gives a delayed/biphasic peak (Focalin XR ≈1.5 h and ≈6.5 h)
Half-life	≈2–4 h (immediate-release, dexmethylphenidate ≈2–4.5 h), apparent duration is longer for extended-release products
V_d	Not reported
Protein binding	≈30%
Metabolism	De-esterified by carboxylesterase CES1A1 to inactive ritalinic acid (the major route, ~80% of the dose). Minimal CYP involvement. Co-ingested ethanol drives transesterification to the active metabolite ethylphenidate and raises d-methylphenidate exposure (by up to ~40%).
Excretion	Renal (largely as ritalinic acid)

Toxicology & Safety

Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Methylphenidate is a first-line ADHD medicine with well-established efficacy and a generally favourable safety profile when prescribed and monitored, but it is a Schedule II/controlled stimulant with real risks. Cardiovascular: it raises heart rate and blood pressure and can cause palpitations. It should be used cautiously (and structural cardiac disease excluded) because rare serious cardiovascular events have been reported. Psychiatric/other: appetite loss, insomnia, anxiety, irritability, headache and, in children, modest slowing of growth. Uncommonly it can precipitate psychosis, mania, tics or seizures. Abuse and diversion occur, especially when tablets are crushed and insufflated or injected: the insoluble fillers in oral formulations damage the nasal mucosa and, if injected, the lungs ('Ritalin lung'/pulmonary talc granulomatosis). It is contraindicated with MAOIs (hypertensive crisis) and should not be combined with other stimulants. Non-medical binge use drives compulsive redosing, a harsh comedown (fatigue, low mood, irritability) and psychological dependence.^[6]^[7]

Legal Status

Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.

US: Schedule II. UK: Class B. DE: BtMG Anlage III

Interactions & Contraindications

Drug interactions

MAOIs Risk of hypertensive crisis, contraindicated including within 14 days.^[6]

Stimulants (amphetamines, cocaine) Additive cardiovascular strain and hyperthermia with other sympathomimetics.^[6]

Alcohol Transesterification to ethylphenidate raises active-drug exposure and adds cardiovascular and impairment risk.^[6]

Other serotonergic drugs At very high stimulant doses a theoretical serotonin-toxicity risk, though methylphenidate itself has little serotonergic action.^[6]

Contraindications

Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent or recent (within 14 days) MAOI use.^[6]

Cardiovascular disease, hypertension or arrhythmia symptomatic disease, structural cardiac abnormalities or serious arrhythmias.^[6]

Hyperthyroidism also phaeochromocytoma.^[6]

Closed-angle glaucoma^[6]

Personal or family history of psychosis, schizophrenia or bipolar disorder marked anxiety or agitation, or a history of psychosis or mania.^[6]

Usage & Context

A first-line prescription stimulant for attention-deficit/hyperactivity disorder (ADHD) in children and adults, and a treatment for narcolepsy. It is taken orally as immediate-release tablets or long-acting formulations (e.g. Concerta OROS, Medikinet/Ritalin LA).
First synthesised in 1944 by Leandro Panizzon at Ciba and marketed as Ritalin from 1954. It became one of the most widely prescribed medicines for childhood ADHD and, from the 2000s, adult ADHD.
Also used non-medically as a purported cognitive/'study' enhancer and as a recreational stimulant. It is a controlled substance in most countries (US Schedule II, UK Class B, DE Anlage III BtMG).

Sources & Evidence

Further Information

More in this subclass