Difference Between Amphetamine and Methylphenidate


Main Difference

The main difference between Amphetamine and Methylphenidate is that Amphetamine is a potent CNS stimulant while Methylphenidate is mild CNS stimulant.

Amphetamine vs. Methylphenidate

Amphetamine is a strong CNS stimulant; on the other hand, Methylphenidate is a mild CNS stimulant. Amphetamine causes mental alertness and increases motor activity while Methylphenidate although causes mental alertness but it has less effect on motor activities. Amphetamine has a half-life of 10 hrs on the other hand Methylphenidate has an elimination half-life of 2-3 hrs. Amphetamine bioavailability after an oral dose is more than 70% while Methylphenidate bioavailability after an oral dose is round about 30%.

Comparison Chart

Amphetamine is a potent CNS stimulant and an indirect-acting sympathomimetic agent.Methylphenidate is a mild CNS stimulant, and chemically is a piperidine derivative.
Role as Dopaminergic Drugs
Amphetamine acts as a dopaminergic drug because it acts as a dopamine releasing agent and dopamine reuptake inhibitor.Methylphenidate acts as a dopaminergic drug because it acts as a norepinephrine-dopamine reuptake inhibitor.
Controlled Substance
Amphetamine is a schedule II controlled drug.Methylphenidate is a schedule II controlled drug.
Duration of Action
3-6 hrs when given orally.2-4 hrs when given orally.
Effect on CNS
Amphetamine is a potent CNS stimulator.Methylphenidate is a mild CNS stimulator.
Drug Interactions
Proton pump inhibitors, H2 receptor antagonist, Tricyclic AntidepressantsAripiprazole, Amphetamine, Dextroamphetamine, Ibuprofen
Amphetamines or its analogs sensitivity, Thickening of artery walls, Minor or severe Hypertension, Bipolar disordersAnemia, Manic-depression, Alcoholism, Psychotic disorders, Hypertension
Adverse Effects
Raynaud’s Syndrome
Rapid Heart Rate
Dry Mouth
Teeth Grinding
Stomach Pain
Loss of Appetite

What is Amphetamine?

Amphetamine is a potent CNS stimulant and an indirect-acting sympathomimetic showing peripheral α and β actions. Amphetamine is chemically a racemic β–phenylisopropylamine. Amphetamine is effective orally, and it possesses a long duration of action. Amphetamine is used to raise both systolic and diastolic blood pressure. Amphetamine shows marked contractile effect on the sphincter of the urinary bladder, so it is used in the treatment of enuresis and incontinence. Amphetamine show different response on gastrointestinal tract in different conditions i-e in case of pronounced enteric activity amphetamine relaxes the intestine and causes a delay in the movement of the intestinal contents and if the gut is already relaxed then opposite effect occurs. Amphetamine stimulates medullary respiratory center and increases both the rate and depth of respiration. Amphetamine causes a psychic effect, and its extent depends upon the dose and mental state of persons. Amphetamine causes wakefulness, alertness, and a decreased sense of fatigue. Amphetamine elevates the mood and enhances the ability to concentrate. Amphetamine increases self-confidence and motor and speech activities. Amphetamine causes euphoria and improves simple mental tasks. Amphetamine also improves physical performance, and for this purpose, amphetamine is the drug of abuse. Amphetamine exhibits a little analgesic effect. Amphetamine is also used to treat obesity as it depresses the appetite by acting on lateral hypothalamic feeding. Amphetamine shows toxic effects when there is an overdose of it occurs.



Examples of famous brands containing Amphetamine are Dyanavel and Evoker

What is Methylphenidate?

Methylphenidate is chemically a piperidine derivative and structurally resemble amphetamines. Methylphenidate is a mild CNS stimulant pharmacologically. Methylphenidate is available as Methylphenidate HCl. Methylphenidate is a racemic mixture of its positive and negative enantiomer. Methylphenidate is schedule II controlled drug. Methylphenidate is used to treat attention deficit hyperactivity disorder. Methylphenidate increases the ability of the brain to focus. Methylphenidate combats fatigue. Methylphenidate also increases the brain’s ability to pay more attention and helps to control the problems of behavior. Methylphenidate can treat narcolepsy. Methylphenidate is taken orally and depending upon the condition of patient Methylphenidate is prescribed 2 or 3 times a day. The dose can be adjusted according to the response of a patient i-e dose can be increased or decreased. Methylphenidate is taken on an empty stomach and at least half an hour before eating anything. Methylphenidate should be taken strictly according to prescribed dose as an overdose of Methylphenidate can cause death or disturbed breathing. Methylphenidate is a prescription drug, so pharmacy cannot issue this drug without prescription as it is illegal. Methylphenidate is a norepinephrine-dopamine inhibitor, so Methylphenidate causes euphoria. Methylphenidate modulates the level of dopamine and norepinephrine. Methylphenidate is rapidly absorbed when given through mouth. Methylphenidate peak plasma concentration is reached in 2 hrs. Methylphenidate is although a well-tolerated in spite of this, it shoes some adverse effects like loss of appetite, dry mouth, and anxiety.


Examples of famous brands containing Methylphenidate are Ritalin, Concerta, Inspiral

Key Differences

  1. Amphetamine is a strong CNS stimulant; on the other hand, Methylphenidate is a mild CNS stimulant.
  2. Amphetamine increases both mental alertness and motor activity while Methylphenidate increases only mental activity.
  3. Amphetamine bioavailability after an oral dose is more than 70% whereas Methylphenidate bioavailability after an oral dose is approximately 30%.


The conclusion of the above discussion is that Amphetamine and Methylphenidate both are important for their use to treat ADHD and to enhance mental alertness.

Janet White

Janet White is a writer and blogger for Difference Wiki since 2015. She has a master's degree in science and medical journalism from Boston University. Apart from work, she enjoys exercising, reading, and spending time with her friends and family. Connect with her on Twitter @Janet__White