Methylphenidate
Systematic (IUPAC) name
methyl 2-phenyl-2-(2-piperidyl)acetate
Identifiers
CAS number	113-45-1
ATC code	N06BA04
PubChem	4158
DrugBank	APRD00657
Chemical data
Formula	C14H19NO2
Mol. mass	233.306 g/mol
Pharmacokinetic data
Bioavailability	11–52%
Metabolism	Liver
Half life	2–4 hours
Excretion	Urine
Therapeutic considerations
Pregnancy cat.	C
Legal status	Class B(UK) Schedule II(US)
Routes	?

Indicated for: ADD ADHD narcolepsy Recreational uses: Stimulant / "Speed" / "Uppers" Other uses: treatment-resistant depression appetite suppressant antidepressant augmentation

Contraindications: Use of tricyclic antidepressants (e.g. desipramine), as methylphenidate may dangerously increase their plasma concentrations, leading to potential toxic reactions (mainly, cardiovascular effects). Use of MAO Inhibitors, such as phenelzine (Nardil) or tranylcypromine (Parnate), and certain other drugs. methylphenidate should not be given to patients who suffer from the following conditions: Severe Arrhythmia, Hypertension or Liver damage. Drug-seeking behaviour Pronounced agitation or nervousness

Side effects: Atypical sensations: Cardiovascular: Tachycardia[citation needed] Arterial hypertension[citation needed] Ear, nose, and throat: Endocrinal: Appetite loss Eye: Blurred vision[citation needed] Gastrointestinal: Nausea/vomiting, abdominal pain[citation needed] Hematological: Musculoskeletal: Muscle twitches[citation needed] Neurological: Insomnia, drowsiness, dizziness[citation needed], headache Psychological: Nervousness Euphoria[citation needed] Respiratory: Increased respiration rate Skin: Urogenital and reproductive: Miscellaneous:

Methylphenidate (MPH) is an amphetamine-like prescription stimulant commonly used to treat Attention-deficit hyperactivity disorder (ADHD) in children and adults. It is also one of the primary drugs used to treat symptoms of traumatic brain injury and the daytime drowsiness symptoms of narcolepsy and chronic fatigue syndrome. Brand names of drugs that contain methylphenidate include Ritalin (Ritalina, Rilatine, Ritalin LA (Long Acting)), Attenta, Concerta (a timed-release capsule), Metadate, Methylin and Rubifen. Focalin is a preparation containing only dextro-methylphenidate, rather than the usual racemic dextro- and levo-methylphenidate mixture of other formulations. A newer way of taking methylphenidate is by using a transdermal patch (under the brand name Daytrana), similar to those used for birth control and nicotine release.

Contents 1 History 2 Pharmacology 3 Effects 3.1 Side effects 3.2 Long-term effects 3.2.1 Brain and body 3.2.2 Stature 3.2.3 Risk of death 4 Delivery 5 Criticism 6 Trivia 7 See also 8 Footnotes 9 External links

History

Methylphenidate was patented in 1954 by the Ciba pharmaceutical company (one of the predecessors of Novartis) and was initially prescribed as a treatment for depression, chronic fatigue, and narcolepsy, among other ailments. Beginning in the 1960s, it was used to treat children with ADHD, known at the time as hyperactivity or minimal brain dysfunction (MBD). Today methylphenidate is the medication most commonly prescribed to treat ADHD around the world. According to most estimates, more than 75 percent of methylphenidate prescriptions are written for children, with boys being about four times as likely to take methylphenidate as girls. Production and prescription of methylphenidate rose significantly in the 1990s, especially in the United States, as the ADHD diagnosis came to be better understood and more generally accepted within the medical and mental health communities.

Most brand-name Ritalin is produced in the United States, although methylphenidate is also produced in Mexico and Argentina by respective contract pharmaceutical manufacturers and is most commonly marketed under the brand name "Ritalin" for Novartis. In the United States, various generic forms of methylphenidate are also produced by several pharmaceutical companies (such as Methylin, etc.), and Ritalin is also sold in the United Kingdom, Germany, and other European countries (although in much lower volumes than in the United States). These generic versions of methylphenidate tend to outsell brand-name "Ritalin" four-to-one. In Belgium the product is sold under the name "Rilatine" for Novartis.

Another medicine is Concerta, a once-daily extended release form of methylphenidate, which was approved in April 2000. Studies have demonstrated that long-acting methylphenidate preparations such as Concerta are just as effective, if not more effective, than IR (instant release) formulas.^[1][2][3][4] Time-release medications are also harder to misuse.

In April 2006, the FDA approved a transdermal patch for the treatment of ADHD, called Daytrana. The once-daily patch administers methylphenidate in doses of 10, 15, 20, or 30mg.^[5] However, the patch must be applied several hours before the effect is desired, and the drug's effect remains for several hours after removal, making it necessary to remove the patch in the mid-to-late afternoon or else insomnia may result.

Pharmacology

Methylphenidate has binding affinity for both the Dopamine transporter and Norepinephrine transporter, with the D-isomer displaying a prominent affinity for the latter. Both the dextro- and levorotary isomers displayed receptor affinity for the serotonergic 5HT(1a) and 5HT(2b) subtypes, though direct binding to the Serotonin transporter was not observed. ^[6]

The isomeric profiles and relative usefulness of dextro- and levo-methylphenidate is analogous to what is found in amphetamine, where dextro-amphetamine is considered to have a more beneficial effect than levo-amphetamine. Dextro-methylphenidate, the active enantiomer, is considered to provide the pharmacological effect of mental focus.^{[citation needed]}

Effects

Methylphenidate is a central nervous system (CNS) stimulant. It is claimed to have a 'calming' effect on many children who have ADHD, reducing impulsive behavior, and helps them concentrate on schoolwork and other tasks. Adults who have ADHD often claim that methylphenidate increases their ability to focus on tasks and organize their lives.

Methylphenidate has been found to have a lower incidence of side-effects compared with dextroamphetamine, a less commonly prescribed medication.^[7] When prescribed at the correct dosage, methylphenidate is usually well-tolerated by patients.^[1]

The means by which methylphenidate helps people with ADHD are not well understood. Some researchers have theorized that ADHD is caused by a dopamine imbalance in the brains of those affected. Methylphenidate is a dopamine reuptake inhibitor, which means that it increases the level of the dopamine neurotransmitter in the brain by partially blocking the transporters that remove it from the synapses.^[8] An alternate explanation which has been explored is that the methylphenidate affects the action of serotonin in the brain^[9].

In the United States, methylphenidate is classified as a Schedule II controlled substance, the designation used for substances that have a recognized medical value but which have a high potential for abuse because of their addictive potential. Internationally, methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances.^[10] Methylphenidate has been used illegally by students for whom the drug has not been prescribed, to assist with coursework and examinations.^[11] The use of ADHD medication has not been studied for children under the age of 6. ADHD is a condition includes symptoms such as hyperactivity, problems holding still, and following directions, which is also typical of a child under the age of 6. For this reason it may be more difficult to diagnosis a children under this age and caution should be used with this age group.^[12]

Side effects

Reported side effects include difficulty sleeping, stomach aches, headaches, and dry mouth.^{[13] [14]}

Less common side effects include palpitations, high blood pressure and pulse changes. A more comprehensive list of rare side-effects may be found on Medline.^[15]

Long-term effects

Brain and body

In a 2005 study, only "minimal effects on growth in height and weight were observed" after 2 years of treatment. "No clinically significant effects on vital signs or laboratory test parameters were observed." ^[16]

A 2006 review assessing the safety of methylphenidate on the developing brain found that in animals with psychomotor impairments, structural and functional parameters of the dopamine system were improved with treatment ^[17]. This indicates that in subjects with ADHD, methylphenidate treatment may positively support brain development.

A 2003 study tested the effects of d-methylphenidate (Focalin), l-methylphenidate, and d, l-methylphenidate (Ritalin) on mice to search for any carcinogenic effects. The researchers found that all three compounds were non-genotoxic and non-clastogenic; d-MPH, d, l-MPH, and l-MPH did not cause mutations or chromosomal aberrations. They concluded that none of the compounds present a carcinogenic risk to humans.^[18].

In February 2005, a team of researchers from The University of Texas M. D. Anderson Cancer Center led by R.A. El-Zein announced that a study of 12 children indicated that methylphenidate may be carcinogenic. In the study, 12 children were given standard therapeutic doses of methylphenidate. At the conclusion of the 3 month study, all 12 children displayed significant, treatment induced chromosomal aberrations. The researchers indicated that while their study was relatively small, they indicated the results should be reproduced one more time in a bigger population for a definitive conclusion about the genotoxicity of methylphenidate to be drawn. ^[19] This is the first study of this kind ever performed in humans.

Stature

Researchers have also looked into the role of methylphenidate in affecting stature, with some studies finding slight decreases in height acceleration.^[20] Other studies indicate height may normalize by adolescence.^[21][22]

Risk of death

There have been at least 19 cases of Cardiac arrest in children taking methylphenidate, leading to calls by the Drug Safety and Risk Management Advisory Committee to the FDA to require the most serious type of health warning on the label, but this advice was rejected (New Scientist 18 Feb. 2006).

On February 9, 2006, the Drug Safety and Risk Management Advisory Committee of the Food and Drug Administration (FDA) voted by a margin of eight to seven to recommend a "black-box" warning describing the cardiovascular risks of stimulant drugs used to treat attention deficit/hyperactivity disorder (ADHD). On March 22, 2006 the FDA Pediatric Advisory Committee decided that the medications do not need "black box" warnings about their risks. The FDA declined to include these black box warnings upon review.^{[citation needed]}

Delivery

Ritalin: 5 mg, 10 mg, and 20 mg tablets;
Ritalin SR: 20 mg tablets;
Ritalin LA: 10 mg, 20 mg, 30 mg, and 40 mg capsules;
Attenta: 10mg tablets;
Methylin: 5 mg, 10 mg, and 20 mg tablets;
Methylin ER: 10 mg and 20 mg tablets;
Metadate ER: 10 mg and 20 mg tablets;
Metadate CD: 10 mg, 20 mg, 30 mg, and 60 mg capsules;
Concerta: 18 mg, 27 mg, 36 mg, 54 mg, and 72 mg tablets;
Equasym: 5 mg and 10 mg tablets;
Rubifen: 5 mg, 10 mg, and 20 mg tablets;
Daytrana: 10 mg, 15 mg, 20 mg, and 30 mg patches

Criticism

Main article: Controversy about ADHD

Methylphenidate is frequently used in the treatment for ADHD, and as such criticism of methylphenidate is related to the controversy about ADHD. Generally criticism of Methylphenidate revolves around the alleged or real side effects, illict use of the drug, questionable addiction issues, and the ethics of giving Methylphenidate to children to reduce symptoms.

Trivia

The mathematician Paul Erdős took methylphenidate and other stimulants for much of his life.^[23] He stopped for a month in response to a bet that he would be unable to. Afterwards, he said that his work had been set back by a month. He described his time of abstention by saying "Before, when I looked at a piece of blank paper my mind was filled with ideas. Now all I see is a blank piece of paper."^[24]

Professional wrestler Shane McMahon suffered from Attention Deficit Disorder, for which he had to take Ritalin. ^[25]

The song "Vitamin R (Leading Us Along)" by the American alternative metal band Chevelle, was written about a friend of the band who became addicted to methylphenidate and exhibited deviant behavior.

Bart Simpson is given Ritalin and Ritalin-like medicine in the episode Brother's Little Helper.

See also

• Dexmethylphenidate (Focalin)
• Phenethylamines
• Psychoactive drug
• Stimulant
• Amphetamine
• Methamphetamine
• Benzedrine
• Attention Deficit Disorder

Footnotes

External links

• Ritalin(R) 10mg Consumer Medicine Information (Australia)
• Information from the manufacturer on the methylphenidate ADHD Patch
• U.S. Drug Enforcement Administration statement on methylphenidate abuse
• Dep't of Energy 1998 Sep 29 press release on Ritalin
• Children and Medication � a multimodal presentation
• Students without ADHD are using Ritalin to help them study