Stimulants: Methylphenidates

Methylphenidate

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 NameBrand NameUsual Starting DoseTypical Daily Dose Range
Long-acting MPHRitalin SR20mg QAM10-140mg
Ritalin LA20mg QAM20-120mg
Concerta18mg QAM18-144mg
Metadate CD10-20mg QAM10-120mg
Short-acting MPHMethylphenidate 10mg q4hrs10-140mg
Methylin10mg q4hrs10-140mg
Ritalin10mg q4hrs10-140mg
D-methylphenidate Focalin5mg q4-6hrs10-80mg
Focalin XR5-10mg QAM10-80mg
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)

 

Notable Interactions:

  • 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:

  • Insomnia
  • Headache
  • Anxiety/Nervousness
  • Abdominal Pain
  • Anorexia
  • Nausea
  • Vomiting
  • Dry Mouth
  • Weight loss
  • Seizures (rarely with PO)
  • Psychosis (rarely with PO)
  • Elevated Blood Pressure
  • Tachycardia
  • Sudden death has been reported in patients with preexisting cardiac structural abnormalities

 

 

FDA INDICATIONS:

1) Attention Deficit Hyperactivity Disorder in children and adults

2) Narcolepsy (Ritalin, Concerta, Ritalin-SR, Ritalin-LA)

 

Additional Information

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.

References

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