Methylphenidate was first synthesized in 1944 by the CIBA Pharmaceutical company. In the 1960s and 1970s, Methylphenidate was first marketed for “hyperkinetic syndrome” (now known as ADHD), narcolepsy, and depression. Methylphenidate, like many other stimulants (e.g., cocaine) binds to, and inhibits, the dopamine transporter (DAT) on dopaminergic neurons and the norepinephrine transporter (NET) on norepinephrine neurons in the brain. Inhibition of DAT and NET increases extracellular levels of dopamine and norepinephrine, respectively, in target areas of the brain. Methylphenidate is primarily used to treat Attention Deficit Hyperactivity Disorder, Narcolepsy, Depression, and Chronic Fatigue. Methylphenidate comes in a number of formulations with different durations of action. Brand names for methylphenidate-based medications include Focalin, Ritalin, Metadate, Concerta, Daytrana, and Methylin
Methylphenidate (Ritalin, Concerta)
|Generic Name||Brand Name||Usual Starting Dose||Typical Daily Dose Range|
|Long-acting MPH||Ritalin SR||20mg QAM||10-140mg|
|Ritalin LA||20mg QAM||20-120mg|
|Metadate CD||10-20mg QAM||10-120mg|
|Short-acting MPH||Methylphenidate||10mg q4hrs||10-140mg|
|Focalin XR||5-10mg QAM||10-80mg|
|MPH, Methylphenidate; XR, Extended Release; SR, Sustained Release; LA, Long-Acting|
HALF-LIFE: 2-4 hours
TIME TO EFFECT: IR ~15-30min | Concerta/LA/SR ~1-2 hours
PEAK IN PLASMA: IR 1-2 hours | Concerta/LA/SR ~5-8 hours
DURATION OF CLINICAL ACTION: IR 4-5 hours |Concerta/LA/SR ~ 8-12 hours
METABOLISM: Primarily Liver and Gut
WITH/WITHOUT FOOD: Methylphenidate is absorbed at a faster rate in the presence of food
STARTING DOSE: (See Table Above)
TARGET DOSING RANGE: (See Table Above)
BEST TIME TO DOSE: Morning
PREGNANCY: Avoid if possible (discuss with a medical professional)
BREASTFEEDING: Avoid if possible (discuss with a medical professional)
Desipramine should be used with extreme caution if used with methylphenidate
Antacids increase absorption of methylphenidate
Dopamine antagonists such as haloperidol and chlorpromazine as well as lithium may inhibit stimulant effects
Avoid using with monoamine oxidase inhibitors (MAOIs) due to risk of hypertensive crises and malignant hyperthermia
Notable Side Effects:
Seizures (rarely with PO)
Psychosis (rarely with PO)
Elevated Blood Pressure
Sudden death has been reported in patients with preexisting cardiac structural abnormalities
1) Attention Deficit Hyperactivity Disorder in children and adults
2) Narcolepsy (Ritalin, Concerta, Ritalin-SR, Ritalin-LA)
Methylphenidate has four (4) possible stereoisomers because it has two (2) stereoactive centers. Dexmethylphenidate (brand name Focalin) is the most biologically active form and also 2x more potent than methylphenidate. Methylphenidates generally have fewer adverse effects compared to amphetamines. Methylphenidate was synthesized by CIBA (now Novartis) pharmaceuticals by chemist Leandro Panizzon, whose wife, Rita, used it for her chronic low blood pressure. Leandro named the drug “Ritaline” after his wife.
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