Table of Contents
What are Stimulants?
The term “stimulant” is a bit nebulous. Generally, stimulants refer to medications that promote attention and arousal. They include medications used to treat narcolepsy, daytime fatigue, and attention deficit hyperactivity disorder.
The stimulants include the amphetamines (dextroamphetamine, amphetamine mixed salts, lisdexamfetamine, methamphetamine), methylphenidates (ritalin, concerta), modafinil (Provigil) and armodafinil (Nuvigil).
Amphetamine and methylphenidate primarily promote dopamine and norephinephrine neurotransmission in specific areas of the brain whereas modafinil and armodafinil primarily promote histamine release.
Overview of Methylphenidate
Methylphenidate was first synthesized in 1944 by the CIBA Pharmaceutical company’s chemist Leandro Panizzon. Panizzon’s wife, Rita, used it for her chronic low blood pressure and therefore Panizzon named the drug “Ritaline” after his wife.
In the 1960s and 1970s, Methylphenidate was first marketed for “hyperkinetic syndrome” (now known as ADHD), narcolepsy, and depression. 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
PROTEIN BINDING: Low (15%)
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 Hepatic (liver) via carboxylesterase CES1A1 (not CYP mediated) 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)
Mechanism of Action
Methylphenidate, like cocaine, binds to and inhibits both the norepinephrine transporter (NET) and the dopamine transporter (DAT) on noradrenergic neurons and dopaminergic neurons in the brain, respectively. Inhibition of NET and DAT increases extracellular levels of norepinephrine (NE) and dopamine (DA), respectively, in specific areas of the brain. Methylphenidate, unlike amphetamines, does not facilitate release of dopamine and norepinephrine by reversing the mechanism of the dopamine and norepinephrine transporters.
- 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
- Abdominal Pain
- Dry Mouth
- Weight loss
- Seizures (rarely with PO)
- Psychosis (rarely with PO)
- Elevated Blood Pressure
- Sudden death has been reported in patients with preexisting cardiac structural abnormalities
- Attention Deficit Hyperactivity Disorder in children and adults
- 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 is also twice as potent as methylphenidate. Methylphenidate generally has fewer adverse effects compared to amphetamine but may not be as effective.
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