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Ritalin



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), Concerta (a timed-release capsule), Metadate, Methylin and Rubifen. Focalin is a preparation containing only dextro-methylphenidate, rather than the usual racemic dextro- and laevo-methylphenidate mixture of other formulations.


History


Ritalin Drug
Methylphenidate was patented in 1954 by the Ciba Pharmaceutical Company (a precursor to 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 the United States).

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.

Effects
Methylphenidate is a central nervous system (CNS) stimulant. It has a "calming" effect on many children who have ADHD, reducing impulsive behavior and the tendency to "act out", and helps them concentrate on schoolwork and other tasks. Adults who have ADHD often find that MPH increases their ability to focus on tasks and organize their lives.

Methylphenidate has been found to have a lower incidence of side-effects compared to dextroamphetamine, a less commonly perscribed medication.

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. MPH 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.

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. Internationally, methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances. Some people abuse MPH by crushing the tablets and snorting them, the "high" resulting from the increased rate of dopamine transporter blockade due to quicker absorption into the bloodstream. In this manner, the effect of Ritalin is similar to that of cocaine or amphetamine and such abuse can lead to addiction. When taken orally in prescribed doses, MPH has a low addiction liability and rarely produces a "high".

Methylphenidate is rumored to be used by some students as a stimulant to assist with coursework and examinations.

Some may use it recreationally in combination with alcohol to attempt to counter the downing effects of excessive drinking, presumably allowing the user to stay fairly awake and social while heavily intoxicated. However, there is no scientific evidence to substantiate the validity of this claim, and the behavior could have serious negative consequences.

Formulations
Most products containing methylphenidate contain a 50:50 racemic mixture of dextro-methylphenidate and levo-methylphenidate, although it is only dextro-methylphenidate, the active enantiomer, which is considered to provide the pharmacologically useful effects of mental focus. However, with the introduction of Focalin, pure dextro-methylphenidate is available. Described as a fast-acting form of the drug, it is absorbed more quickly by the body, with a shorter time to peak concentration (and excretion) than with the heterogeneous compound.

The pharmacological 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.

Overprescription
Some consider the treatment of children with stimulant medication to be controversial since the number of children taking them has increased dramatically over the years. Critics contend that MPH is extensively overprescribed in the United States, especially among children, and that it transforms healthy children into "zombies", stifling their creativity and intellectual energy .

However, criticism that methylphenidate is overprescribed may be unfounded; the incidence of ADHD is believed to be between three and five percent of the population, while the number of children in America taking Ritalin is estimated at one to two percent. In a sense, the drug could be both overprescribed and underprescribed; that is, some children taking MPH may not benefit from it, while an even greater number of children would benefit from MPH but are not taking it.

Addiction and "Zombification"
Recent research suggests that boys with ADHD who are treated with stimulants like MPH are actually less likely to abuse drugs including alcohol later in life. Also, the only time when the usage of the drug is known to induce zombie-like effects (known to parents and those familiar with the drug as "zombie syndrome" or "zombification") is in an overdose situation. When prescribed at the correct dosage, methylphenidate is usually well-tolerated by patients.

Long-term effects
As long-term use of methylphenidate was relatively uncommon before the 1990s, the long-term neurological effects are not well researched. As documented for amphetamines, the potential of methylphenidate use over many years causing permanent neurological damage to dopaminergic systems exists at least in theory. For example, Adriani et al (2005) found plastic changes in reward related behavior in rats after they were in a drug-free state. Whether or not this would have any effect on human cognition is unknown.

In a 2005 study, no "clinically significant" effects on growth, vital signs, tics, or laboratory tests (including urinalysis, hematology/complete blood counts, electrolytes, and liver function tests) were observed after 2 years of treatment.

Effects on stature
Researchers have also looked into the role of methylphenidate in affecting stature, with some studies finding slight decreases in height acceleration. Other studies indicate height may normalize by adolesence.

Risk of death
Although extremely uncommon, Ritalin has been found by coroners to be the cause of a few deaths among children.

Potential Carcinogen
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 small scale 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 researches indicated that while their study was too small to derive meaningful conclusions, they indicated more studies should be done as the link between chromosomal aberrations and cancer is well documented.

The results are controversial, however, since there have been conflicting results regarding the mutagenicity of methylphenidate.

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 chromosome abberations. They concluded that none of the compounds present a carcinogenic risk to humans.

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