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Methylphenidate (MPH) is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, Postural Orthostatic Tachycardia Syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult, and obesity. Methylphenidate belongs to the piperidine class of compounds and increases the levels of dopamine and norepinephrine in the brain through reuptake inhibition of the monoamine transporters. MPH possesses structural similarities to amphetamine, and though it is less potent, its pharmacological effects are even more closely related to those of cocaine. MPH is most commonly known by the trademark name Ritalin, which is an instant-release racemic mixture, although a variety of formulations and generic brand names exist.

History

Methylphenidate was first synthesized in 1944, and was identified as a stimulant in 1954.

Originally it was marketed as a mixture of two racemates, 80% (±)-erythro and 20% (±)-threo. Subsequent studies of the racemates showed that the central stimulant activity was associated with the threo racemate and were focused on the separation and interconversion of the erythro isomer into the more active threo isomer.

Beginning in the 1960s, it was used to treat children with ADHD or ADD, known at the time as hyperactivity or minimal brain dysfunction (MBD). Today methylphenidate is the most commonly prescribed medication to treat ADHD around the world. Production and prescription of methylphenidate rose significantly in the 1990s, especially in the United Statesmarker, 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 Statesmarker, and methylphenidate is produced in the United States, Mexicomarker, Argentinamarker and Pakistanmarker. Other generic forms, such as "methylin", are produced by several U.S. pharmaceutical companies. Ritalin is also sold in the United Kingdommarker, Germanymarker 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" and in Brazil and Portugal as "Ritalina".

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. Certain time-release medications are also less prone to abuse as they are not easily crushed for abuse.

In April 2006, the U.S. Food and Drug Administration (FDA) approved a transdermal patch for the treatment of ADHD called Daytrana.

Therapeutic uses

Methylphenidate 10 mg Tablet (Mallinckrodt)
TMP is the most commonly prescribed psychostimulant and works by increasing the activity of the central nervous system. It produces such effects as increasing or maintaining alertness, combating fatigue, and improving attention. The benefits and cost effectiveness of methylphenidate long term are unknown due to a lack of research. The long term effects of methylphenidate on the developing brain are unknown. Methylphenidate is not approved for children under six years of age.

Attention deficit hyperactivity disorder

TMP is approved by the FDA for the treatment of attention-deficit hyperactivity disorder The addition of behavioural modification therapy (e.g. CBT) has additional benefits on treatment outcome. There is a lack of evidence of the effectiveness in the long term of beneficial effects of methylphenidate with regard to learning and academic performance. A meta analysis of the literature concluded that methylphenidate quickly and effectively reduces the signs and symptoms of ADHD in children under the age of 18 in the short term but found that this conclusion may be biased due to the high number of low quality clinical trials in the literature. There have been no placebo controlled trials investigating the long term effectiveness of methylphenidate beyond 4 weeks thus the long term effectiveness of methylphenidate has not been scientifically demonstrated. Serious concerns of publication bias regarding the use of methylphenidate for ADHD has also been noted. A diagnosis of ADHD must be confirmed and the benefits and risks and proper use of stimulants as well as alternative treatments should be discussed with the parent before stimulants are prescribed. The dosage used can vary quite significantly from individual child to individual child with some children responding to quite low doses whereas other children require the higher dose range. The dose therefore should be titrated to an optimal level which achieves therapeutic benefit and minimal side effects. Therapy with methylphenidate should not be indefinite. Weaning off periods to assess symptoms are recommended.

Narcolepsy

Narcolepsy, a chronic sleep disorder characterized by overwhelming daytime drowsiness and sudden attacks of sleep, is treated primarily with stimulants. Methylphenidate is considered effective in increasing wakefulness, vigilance, and performance. Methylphenidate improves measures of somnolence on standardized tests, such as the Multiple Sleep Latency Test, but performance does not improve to levels comparable to healthy controls.

Adjunctive

Use of stimulants such as methylphenidate in cases of refractory depression is controversial. In individuals with cancer, methylphenidate is commonly used to counteract opioid-induced somnolence, to increase the analgesic effects of opioids, to treat depression, and to improve cognitive function. Methylphenidate may be used in addition to an antidepressant for treatment-refractory major depressive disorder. It can also improve depression in several groups including stroke, cancer, HIV-positive patients. However, benefits tend to be only partial with stimulants being generally less effective than traditional antidepressants and there is some suggestive evidence of a risk of habituation. Stimulants may however, have fewer side effects than tricyclic antidepressants in the elderly and medically ill. A review of the literature found that methylphenidate was ineffective for refractory cases of major depression.

Substance dependence

Methylphenidate has shown some benefits as a replacement therapy for methamphetamine addicts. Methylphenidate and amphetamine have been investigated as a chemical replacement for the treatment of cocaine dependence in the same way that methadone is used as a replacement for heroin. Its effectiveness in treatment of cocaine or other psychostimulant dependence has not been proven and further research is needed.

Early research began in 2007-8 in some countries on the effectiveness of methylphenidate as a substitute agent in refractory cases of cocaine dependence. That it can satisfy cravings for cocaine in a way which is subjectively and pharmacologically equivalent but longer-lasting as well as easier on the body and somewhat safer and easier to manage has long been part of the 'street lore' associated with stimulants in many parts of the world. Methylenedioxymethcathinone (another closely related phenethylamine derived stimulant) shows particular potential for this application due to its closer similarity to the effect of cocaine than amphetamine. This is similar to the way that other substitution drugs such as methadone, buprenorphine, LAAM, butorphanol, extended-release oral morphine, dihydrocodeine, and clonidine were amongst opioid users in various times over the past century.

Pervasive developmental disorders

Given the high co-morbidity between ADHD and autism, a few studies have examined the efficacy and effectiveness of methylphenidate in the treatment of autism. However, most of these studies examined the effects of methylphenidate on attention and hyperactivity symptoms among kids with autism spectrum disorders. Aman and Langworthy (2000) attempted to examine the effects of methylphenidate on social-communication and self-regulation behaviors among kids with ASDs.

The sample included 33 children with pervasive developmental disorder (29 boys) with a mean age of 6.93 years (range 5-13). This was a 4-week randomized, double-blind, cross-over placebo study, with treatment changing each week between 4 conditions: placebo, low dose, medium dose, and high dose. In this design, neither the experimenters nor the families know which of the 4 treatments the child is receiving at any given time. In addition, the treatment condition changes randomly each week, without anyone knowing the nature of the old or new condition. This allows the experimenters to assume that consistent changes in behaviors that occur during a particular treatment is truly due to the effect of that treatment and not to the expectation of the treatment (placebo effect).

The results indicate that children showed significantly more joint attention behaviors when receiving methylphenidate than when receiving the placebo (although the most effective dosage varied by individual). Furthermore, at a group level, the low dose of methylphenidate resulted in significantly improved joint attention behaviors when compared to the placebo, but no differences were noted between the low, medium, and high doses. Low and medium doses of methylphenidate also resulted in improved self-regulation behavior when compared to placebo.

The study presents compelling preliminary evidence suggesting that methylphenidate is effective in improving some social behaviors among children with autism spectrum disorders.

Investigational

Animal studies using rats with ADHD like behaviours were used to assess the safety of methylphenidate on the developing brain and found that psychomotor impairments, structural and functional parameters of the dopaminergic system were improved with treatment. This animal data suggests that methylphenidate supports brain development and hyperactivity in children diagnosed with ADHD. However, in normal control animals methylphenidate caused long lasting changes to the dopaminergic system suggesting that if a child is misdiagnosed with ADHD they may be at risk of long lasting adverse effects to brain development. Animal tests found that rats given methylphenidate grew up to be more stressed and emotional. It is unclear due to lack of followup study whether this occurs in ADHD like animals and whether it occurs in humans. However, long lasting benefits of stimulant drugs have not been found in humans.

Methylphenidate may reduce the risk of falls in older adults by treating cognitive deficits associated with aging and disease.

Delivery formulations

Ritalin 10 mg pill (Ciba/Novartis)
All media are in milligrams. Ritalin is mostly administered in the form of a tablet or capsule.

Tablets

  • Ritalin: 5, 10 or 20 mg tablets.
  • Ritalin SR: 20 mg controlled-release tablets.
  • Attenta: 10 mg tablets.
  • Methylin: 5, 10 or 20 mg tablets.
  • Methylin ER: 5, 10 and 20 mg controlled-release tablets.
  • Metadate ER: 10 and 20 mg controlled-release tablets.
  • Equasym: 5, 10, 20 or 30 mg tablets.
  • Rubifen: 5, 10 or 20 mg tablets.
  • Motiron: 5, 10 or 20 mg tablets.


Capsules

  • Concerta: 18, 27, 36, and 54 mg osmotic controlled release capsules. (goes off patent in 2018)

    Note: Some adults may take two 36 mg capsules for an effective dose of 72 mg.
  • Ritalin LA: 10, 20, 30 or 40 mg controlled-release capsules.
  • Metadate CD: 10, 20, 30, 40, 50 or 60 mg controlled-release capsules.
  • Biphentin: 10, 15, 30, 40, or 60 mg suspended release capsules.


Patches

  • Daytrana 10, 15, 20 or 30 mg controlled-release patches (1.1, 1.6, 2.2 or 3.3 mg/hour for 9 hours).


Adverse effects

Some adverse effects may emerge during chronic use of methylphenidate so a constant watch for adverse effects is recommended. Some adverse effects of stimulant therapy may emerge during long term therapy but there is very little research of the long term effects of stimulants.

The most common side effects of taking methylphenidate are nervousness and insomnia.Other reactions include:

Known or suspected risks to health

Researchers have also looked into the role of methylphenidate in affectingstature, with some studies finding slight decreases in height acceleration.Other studies indicate height may normalize by adolescence. 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."

A 2003 study tested the effects of dextromethylphenidate (Focalin), levomethylphenidate, and (racemic) dextro-, levomethylphenidate (Ritalin) on mice to search for any carcinogenic effects. The researchers found that all three preparations 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. Current scientific evidence supports that long-term methylphenidate treatment does not increase the risk of developing cancer in humans.

The use of ADHD medication in children under the age of 6 has not been studied. Severe hallucinations may occur. ADHD symptoms include hyperactivity and difficulty holding still and following directions; these are also characteristics of a typical child under the age of 6. For this reason it may be more difficult to diagnose young children, and caution should be used with this age group.

However, it was documented in 2000, by Zito et al.“that at least 1.5% of children between the ages of two and four are medicated with stimulants, anti-depressants and anti-psychotic drugs, despite the paucity of controlled scientific trials confirming safety and long-term effects with preschool children.”

On March 22, 2006 the FDA Pediatric Advisory Committee decided that medications using methylphenidate ingredients do not need black box warnings about their risks, noting that "for normal children, these drugs do not appear to pose an obvious cardiovascular risk." Previously, 19 possible cases had been reported of Cardiac arrest linked to children taking methylphenidate and the Drug Safety and Risk Management Advisory Committee to the FDA recommend a "black-box" warning in 2006 for stimulant drugs used to treat attention deficit/hyperactivity disorder.

Doses prescribed of stimulants above the recommended dose level is associated with higher levels of psychosis, substance misuse and psychiatric admissions.

Long term effects

The effects of long-term methylphenidate treatment on the developing brains of children with ADHD is the subject of study and debate. Although the safety profile of short-term methylphenidate therapy in clinical trials has been well established, repeated use of psychostimulants such as methylphenidate is less clear. The long term effects of methylphenidate such as drug addiction, withdrawal reactions, psychosis and depression and effects in pregnancy has received very little research and thus the long term effects of using stimulants for ADHD are largely unknown . There are no well defined withdrawal schedules for discontinuing long term use of stimulants. There is limited data which suggests that there may be modest benefits in correctly diagnosed children with ADHD but there are also overall modest risks. Short term clinical trials lasting a few weeks show an incidence of psychosis of about 0.1%. A small study of just under 100 children which assessed long term outcome of stimulant use found that 6% of children became psychotic after months or years of stimulant therapy. Typically psychosis would abate soon after stopping stimulant therapy. As the study size was small, larger studies have been recommended. The long term effects on mental health disorders in later life of chronic use of methylphenidate is unknown. Concerns have been raised that long-term therapy might cause drug dependence, paranoia, schizophrenia and behavioral sensitisation, similar to other stimulants. Psychotic symptoms from methylphenidate can include, hearing voices, visual hallucinations, urges to harm oneself, severe anxiety, euphoria, grandiosity, paranoid delusions, confusion, increased aggression and irritability. Methylphenidate psychosis is unpredictable in who it will occur. Family history of mental illness does not predict the incidence of stimulant toxicosis in ADHD children. High rates of childhood stimulant use is found in patients with a diagnosis of schizophrenia and bipolar disorder independent of ADHD. Individuals with a diagnosis of bipolar or schizophrenia who were prescribed stimulants during childhood typically have a significantly earlier onset of the psychotic disorder and suffer a more severe clinical course of psychotic disorder. Knowledge of the effects of chronic use of methylphenidate is poorly understood with regard to persisting behavioral and neuroadaptational effects.

Tolerance and behavioural sensitisation may occur with long term use of methylphenidate. There is also cross tolerance with other stimulants such as amphetamines and cocaine. Stimulant withdrawal or rebound reactions can occur and should be minimised in intensity, i.e. via a gradual tapering off of medication over a period of weeks or months. A very small study of abrupt withdrawal of stimulants did suggest that withdrawal reactions are not typical. Nonetheless withdrawal reactions may still occur in susceptible individuals. The withdrawal or rebound symptoms of methylphenidate can include psychosis, depression, irritability and a temporary worsening of the original ADHD symptoms. Methylphenidate due to its very short elimination half life may be more prone to rebound effects than d-amphetamine. Up to a third of ADHD children experience a rebound effect when methylphenidate dose wears off.

Contraindications

Methylphenidate should not be prescribed concomitantly with tricyclic antidepressants, such as desipramine, or monoamine oxidase inhibitors, such as phenelzine or tranylcypromine, as methylphenidate may dangerously increase plasma concentrations, leading to potential toxic reactions (mainly, cardiovascular effects). Methylphenidate should not be prescribed to patients who suffer from severe arrhythmia, hypertension or liver damage. It shouldn't be prescribed to patients who demonstrate drug-seeking behaviour, pronounced agitation or nervousness. Care should be taken while prescribing methylphenidate to children with a family history of Paroxysmal Supraventricular Tachycardia (PSVT).

Special precautions

Special precaution is recommended in individuals with epilepsy with additional caution in individuals with uncontrolled epilepsy due to the potential for methylphenidate to lower the seizure threshold.

Pregnancy

Use of methylphenidate during pregnancy is not recommended as there is some evidence of developmental effects, particularly neurobehavioral alterations.

Overdose

In 2004, over 8000 methylphenidate ingestions were reported in US poison center data. The most common reasons for intentional exposure were drug abuse and suicide attempts. An overdose manifests in agitation, hallucinations, psychosis, lethargy, seizures, tachycardia, dysrhythmias, hypertension, and hyperthermia. Benzodiazepines may be used as treatment if agitation, dystonia, or convulsions are present. MPH is prescribed at 1/100th of the estimated lethal dose.

Pharmacology

Methylphenidate is a chain substituted amphetamine derivative, although its chemical structure is more closely related to cocaine. Similar to amphetamines and cocaine, a key target of methylphenidate is the dopamine transporter (DAT). Although methylphenidate is an amphetamine derivative subtle differences exist in its pharmacology; amphetamine works as a dopamine transport substrate where as methylphenidate works as a dopamine transport blocker. Methylphenidate is most active at modulating levels of dopamine and to a lesser extent noradrenaline.

Pharmacokinetics

Methylphenidate has both DAT and NET binding affinity, with the dextromethylphenidate enantiomers displaying a prominent affinity for the norepinephrine transporter. Both the dextro- and levorotary enantiomers displayed receptor affinity for the serotonergic 5HT1A and 5HT2B subtypes, though direct binding to the serotonin transporter was not observed.

The enantiomers and the relative psychoactive effects and CNS stimulation of dextro- and levo-methylphenidate is analogous to what is found in amphetamine, where dextro-amphetamine is considered to have a greater psychoactive and CNS stimulatory effect than levo-amphetamine.

Pharmacodynamics

Methylphenidate exerts its therapeutic effects via blocking the reuptake of dopamine into nerve terminals (as well as stimulating the release of dopamine from dopamine nerve terminals) resulting in increased dopamine levels in the synapse. The onset of central nervous system effects occurs rapidly after intake of methylphenidate and persist for about 4 hours. The mechanism of action and chemical structure of methylphenidate is extremely similar to cocaine with usual doses of both drugs occupying 50% of dopamine transporters. However, cocaine effects such as euphoria are rare at doses prescribed clinically.

The means by which methylphenidate affects people diagnosed 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 norepinephrine and dopamine reuptake inhibitor, which means that it increases the level of the dopamine neurotransmitter in the brain by partially blocking the dopamine transporter (DAT) that removes dopamine from the synapses. This inhibition of DAT blocks the reuptake of dopamine and norepinephrine into the presynaptic neuron, increasing the amount of dopamine in the synapse. It also stimulates the release of dopamine and norepinephrine into the synapse. Finally, it increases the magnitude of dopamine release after a stimulus, increasing the salience of stimulus. An alternate explanation which has been explored is that the methylphenidate affects the action of serotonin in the brain. However, benefits with other stimulants which have a different mechanism of action indicates that support for a deficit in specific neurotransmitters is unsupported and unproven by the evidence and remains a speculative hypothesis.

It is commonly asked why a stimulant should be used to treat hyperactivity, which seems paradoxical. However, MRIs of ADHD brains previously drugged with stimulants show decreased activity in the brain centers critical to concentration and impulse control.

One study finds that methylphenidate reduces the increases in brain glucose metabolism during performance of a cognitive task by about 50%. This suggests that, similar to increasing dopamine and norepinephrine in the striatum and prefrontal cortex, methylphenidate may focus activation of certain regions and make the brain more efficient. This is consistent with the observation that stimulant drugs can enhance attention and performance in some individuals. If brain resources are not optimally distributed (for example, in individuals with ADHD or sleep deprivation), improved performance could be achieved by reducing task-induced regional activation. Stimulant delivery when brain resources are already optimally distributed may then adversely affect performance.

A paper published in Biological Psychiatry reports that methylphenidate fine-tunes the functioning of neurons in the prefrontal cortex - a brain region involved in attention, decision-making and impulse control - while having few effects outside it. The team studied PFC neurons in rats under a variety of methylphenidate doses, including one that improved the animals' performance in a working memory task of the type that ADHD patients have trouble completing. Using microelectrodes, the scientists observed both the random, spontaneous firings of PFC neurons and their response to stimulation of the hippocampus. When they listened to individual PFC neurons, the scientists found that while cognition-enhancing doses of methylphenidate had little effect on spontaneous activity, the neurons' sensitivity to signals coming from the hippocampus increased dramatically. Under higher, stimulatory doses, on the other hand, PFC neurons stopped responding to incoming information.

Interactions

Intake of adrenergic agonist drugs or pemoline with methylphenidate increases the risk of liver toxicity. Antidepressants taken in conjunction with methylphenidate may cause hypertension, hypothermia and convulsions. When methylphenidate is coingested with ethanol, a metabolite called ethylphenidate is formed via hepatic transesterification, not unlike the hepatic formation of cocaethylene from cocaine and alcohol. Coingestion of alcohol (ethanol) also increases the blood plasma levels of d-methylphenidate by up to 40%. It is more selective to the dopamine transporter (DAT) than methylphenidate, having approximately the same efficacy as the parent compound, but has significantly less activity on the norepinephrine transporter (NET).

Abuse potential

Legal warning printed on Ritalin carton (AU)
Methylphenidate is a drug of abuse. Methylphenidate like other stimulants increases dopamine levels but at therapeutic doses the increase is slow and thus euphoria does not typically occur except in rare instances. The abuse potential is increased when methylphenidate is crushed and snorted or when it is injected producing effects almost identical to cocaine. Cocaine-like effects can also occur with very large doses taken orally. The dose however, which produces euphoric effects varies between individuals. Methylphenidate is actually more potent than cocaine in its effect on dopamine transporters. Methylphenidate should not be viewed as a weak stimulant as has previously been hypothesised. The primary source of methylphenidate for abuse is diversion from legitimate prescriptions rather than illicit synthesis. Those who use it to stay awake do so by taking it orally, while intranasal and intravenous are the preferred means for inducing euphoria. IV users tend to be adults whose use may cause panlobular pulmonary emphysema. Methylphenidate has a high potential for drug dependence and addictive abuse due to its similarity pharmaologically to cocaine and amphetamines. Abuse of prescription stimulants is higher amongst college students than non-college attending young adults. College students misuse methylphenidate either as a study aid or to stay awake longer. The increased alcohol consumption due to stimulant misuse has additional negative effects on health.

Methylphenidate's pharmacological effect on the central nervous system is almost identical to that of cocaine. Studies have shown that the two drugs are nearly indistinguishable when administered intravenously to cocaine addicts. However, cocaine has a slightly higher affinity for the dopamine receptor in comparison to methylphenidate, which is thought to be the mechanism of the euphoria associated with the relatively short-lived cocaine high. Controversy has surrounded whether methylphenidate is as commonly abused as other stimulants with many believing that its rate of abuse is much lower than other stimulants. However, the majority of studies assessing its abuse potential and drug liking scores have determined that it has a similar abuse potential as cocaine and amphetamine. Reports of users experimenting with mixing methylphenidate with caffeine and benzocaine to produce a powder for insufflation for an even more cocaine-like effect began to appear in the middle 1970s; this is apparently an incrementation upon a mixture known as Toot containing phenylpropanolamine, caffeine, and benzocaine in the search for legal highs. As moderate doses of cocaine have caffeine-like effects and benzocaine produces a slight stimulant effect of its own perhaps 5 per cent the strength of cocaine with a ceiling in that range, the mixture is reported to have at least some of the sought effects.

Legal status

In the United Statesmarker, methylphenidate is classified as a Schedule II controlled substance, the designation used for substances that have a recognized medical value but present a high likelihood for abuse because of their addictive potential. Internationally, methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances. In the United Kingdommarker, methylphenidate is a controlled 'Class B' substance (the same category as Cannabis), and possession without prescription is illegal, with a maximum sentence of prison.

Controversy

Japanese bottle of Ritalin


Methylphenidate (usually referred to by the brand name Ritalin) has been the subject of controversy in relation to its use in the treatment of ADHD. Criticism generally revolves around alleged or established side effects , concerns of illicit use and abuse, and the ethics of giving psychotropic drugs to children to reduce ADHD symptoms. There is growing concern of the widespread use of methylphenidate and its long term effects, which include concerns of life threatening effects. Calls have been made that methylphenidate be severely restricted in its use. The pharmacological effects of methylphenidate, a schedule II drug are almost identical to cocaine and the amphetamines. The abuse pattern of methylphenidate is very similar to cocaine and amphetamines. In 2002, a study showed that rats treated with methylphenidate are more receptive to the reinforcing effects of cocaine. The contention that methylphenidate acts as a gateway drug been discredited by multiple sources, though this point is still under debate. A study found that a group which had received stimulants during childhood showed a higher rate of cocaine abuse in later adulthood—twice that of the other groups, possibly suggesting that stimulant use during childhood was associated with sensitising or predisposing children to cocaine abuse later in life . Smoking tobacco also appeared to increase the risk of cocaine abuse in this population but even after controlling for tobacco exposure cocaine abuse was still significantly higher in adults who had been medicated with stimulants as children. This risk was still present 15 years after stimulant medication exposure.

Controversy also surrounds whether ADHD is a disorder or a personality trait with some in the medical profession believing that it is a myth that hyperactivity is a disorder . They further point out that as a group ADHD children have in general healthy brains with no gross neurological deficits.

Richard Bromfield claims that Ritalin is often prescribed not because of an underlying neurological disorder, but as an easy way to calm down children whose misbehavior actually results from ordinary causes such as bad parenting.

Treatment of ADHD has led to legal actions including malpractice suits regarding informed consent, inadequate information on side effects, misdiagnosis and coercive use of medications by school systems.

Chemistry of MPH

Four isomers of methylphenidate are known to exist. One pair of threo isomers and one pair of erythro are distinguished, from which only d-threo-methylphenidate exhibits the pharmacologically usually desired effects. When the drug was first introduced it was sold as a 3:1 mixture of erythro:threo diastereomers. The erythro diastereomers are also pressor amines. "TMP" is referring only to the threo product that does not contain any erythro diastereomers. Since the threo isomers are energetically favored, it is easy to epimerize out any of the undesired erythro isomers. The drug that contains only dextrorotary methylphenidate is called d-TMP.

Satendra Singh (2000), pages 81-87.

See also



Related drugs


References

External links




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