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Methylphenidate , sold under various trade names, Ritalin being one of the most commonly known, is a central nervous system CNS stimulant of the phenethylamine [3] and piperidine classes that is used in the treatment of attention deficit hyperactivity disorder ADHD and narcolepsy. Medical use began in ; the drug has become increasingly prescribed since the s, when the diagnosis of ADHD became more widely accepted.

ADHD and other similar conditions are believed to be linked to sub-par performance of the dopamine and norepinephrine functions in the brain, primarily in the prefrontal cortex , responsible for executive function e.

Methylphenidate acts by blocking the dopamine transporter and norepinephrine transporter , leading to increased concentrations of dopamine and norepinephrine within the synaptic cleft. This effect in turn leads to increased neurotransmission of dopamine and norepinephrine.

Methylphenidate is a commonly prescribed psychostimulant and works by increasing the activity of the central nervous system. Meta-analyses and systematic reviews of magnetic resonance imaging MRI studies suggest that long-term treatment with ADHD stimulants specifically, amphetamine and methylphenidate decreases abnormalities in brain structure and function found in subjects with ADHD.

Current models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems , [note 1] particularly those involving dopamine and norepinephrine. Methylphenidate may provide possible protection from methamphetamine induced dopamine neuron damage and possible protection from Parkinson disease according to 1 review. Narcolepsy , a chronic sleep disorder characterized by overwhelming daytime drowsiness and sudden need for sleep, is treated primarily with stimulants.

Methylphenidate is considered effective in increasing wakefulness, vigilance, and performance. Methylphenidate may be used in addition to an antidepressant for refractory major depressive disorder. It can also improve depression in several groups including stroke , cancer , and HIV-positive patients.

Excessive doses of methylphenidate, above the therapeutic range, can interfere with working memory and cognitive control. Methylphenidate is contraindicated for individuals using monoamine oxidase inhibitors e. The US FDA gives methylphenidate a pregnancy category of C, and women are advised to only use the drug if the benefits outweigh the potential risks. In , empirical literature included 63 cases of prenatal exposure to methylphenidate across three empirical studies.

Methylphenidate is generally well tolerated. Gastrointestinal adverse effects may include abdominal pain and weight loss. Cardiac adverse effects may include palpitations , changes in blood pressure and heart rate typically mild , tachycardia rapid resting heart rate , and Raynaud's phenomenon reduced blood flow to the hands and feet. Hyperhidrosis increased sweating is common. Chest pain is rarely observed.

There is some evidence of mild reductions in growth rate with prolonged treatment in children, but no causal relationship has been established and reductions do not appear to persist long-term.

The Daytrana patch has a much higher rate of dermal reactions than oral methylphenidate. Methylphenidate can worsen psychosis in psychotic patients, and in very rare cases it has been associated with the emergence of new psychotic symptoms. Libido disorders, disorientation , and hallucinations are very rarely reported. Priapism is a very rare adverse event that can be potentially serious. USFDA-commissioned studies from indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events sudden death , heart attack , and stroke and the medical use of methylphenidate or other ADHD stimulants.

Because some adverse effects may only emerge during chronic use of methylphenidate, a constant watch for adverse effects is recommended. The symptoms of a moderate acute overdose on methylphenidate primarily arise from central nervous system overstimulation; these symptoms include: Pharmacological texts describe methylphenidate as a stimulant with effects, addiction liability, and dependence liability similar to amphetamine , a compound with moderate liability among addictive drugs ; [74] [75] accordingly, addiction and psychological dependence are possible and likely when methylphenidate is used at high doses as a recreational drug.

Methylphenidate has shown some benefits as a replacement therapy for individuals who are addicted to and dependent upon methamphetamine. Its effectiveness in treatment of cocaine or psychostimulant addiction or psychological dependence has not been proven and further research is needed.

Methylphenidate has the potential to induce euphoria due to its pharmacodynamic effect i. Methylphenidate may inhibit the metabolism of coumarin anticoagulants , certain anticonvulsants , and some antidepressants tricyclic antidepressants and selective serotonin reuptake inhibitors. Concomitant administration may require dose adjustments, possibly assisted by monitoring of plasma drug concentrations.

When methylphenidate is coingested with ethanol , a metabolite called ethylphenidate is formed via hepatic transesterification , [91] [92] not unlike the hepatic formation of cocaethylene from cocaine and alcohol. The reduced potency of ethylphenidate and its minor formation means it does not contribute to the pharmacological profile at therapeutic doses and even in overdose cases ethylphenidate concentrations remain negligible.

Methylphenidate primarily acts as a norepinephrine—dopamine reuptake inhibitor NDRI. It is a benzylpiperidine and phenethylamine derivative which also shares part of its basic structure with catecholamines.

Methylphenidate is most active at modulating levels of dopamine DA and to a lesser extent norepinephrine. Both amphetamine and methylphenidate are predominantly dopaminergic drugs, yet their mechanisms of action are distinct. Methylphenidate acts as a norepinephrine—dopamine reuptake inhibitor while amphetamine is both a releasing agent and reuptake inhibitor of dopamine and norepinephrine. Methylphenidate's mechanism of action in the release of dopamine and norepinephrine is fundamentally different from most other phenethylamine derivatives , as methylphenidate is thought to increase neuronal firing rate , [] [] [] [] whereas amphetamine reduces firing rate, but causes monoamine release by reversing the flow of the monoamines through monoamine transporters via a diverse set of mechanisms, including TAAR1 activation and modulation of VMAT2 function, among other mechanisms.

Methylphenidate has both dopamine transporter and norepinephrine transporter binding affinity, with the dextromethylphenidate enantiomers displaying a prominent affinity for the norepinephrine transporter.

Both the dextrorotary and levorotary enantiomers displayed receptor affinity for the serotonergic 5HT 1A and 5HT 2B subtypes, though direct binding to the serotonin transporter was not observed. Methylphenidate may protect neurons from the neurotoxic effects of Parkinson's disease and methamphetamine abuse. The dextrorotary enantiomers are significantly more potent than the levorotary enantiomers, and some medications therefore only contain dexmethylphenidate. Methylphenidate has been identified as a sigma-1 receptor agonist in rats.

Dextromethylphenidate is much more bioavailable than levomethylphenidate when administered orally, and is primarily responsible for the psychoactivity of racemic methylphenidate. Contrary to the expectation, taking methylphenidate with a meal speeds absorption. Methylphenidate is metabolized into ritalinic acid by CES1A1. Dextromethylphenidate is selectively metabolized at a slower rate than levomethylphenidate.

Four isomers of methylphenidate are possible, since the molecule has two chiral centers. One pair of threo isomers and one pair of erythro are distinguished, from which primarily d-threo-methylphenidate exhibits the pharmacologically desired effects. When the drug was first introduced it was sold as a 4: Since the threo isomers are energetically favored, it is easy to epimerize out any of the undesired erythro isomers.

The drug that contains only dextrorotatory methylphenidate is sometimes called d-TMP, although this name is only rarely used and it is much more commonly referred to as dexmethylphenidate , d-MPH, or d-threo-methylphenidate. The concentration of methylphenidate or ritalinic acid , its major metabolite, may be quantified in plasma, serum or whole blood in order to monitor compliance in those receiving the drug therapeutically, to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage.

Generic forms are produced by numerous pharmaceutical companies throughout the world. Currently available forms include a variety of tablets and capsules, an adhesive-based matrix transdermal system transdermal patch , and an oral suspension liquid syrup.

The dextrorotary enantiomer of methylphenidate, known as dexmethylphenidate , is sold as a generic and under the brand names Focalin and Attenade in both an immediate-release and an extended-release form. In some circumstances it may be prescribed instead of methylphenidate, however it has no significant advantages over methylphenidate at equipotent dosages and so it is sometimes considered to be an example of an evergreened drug.

Methylphenidate was originally available as an immediate-release racemic mixture formulation under the Novartis trademark name Ritalin, although a variety of generics are now available, some under other brand names. Extended-release methylphenidate products include:. Concerta tablets are marked with the letters "ALZA" and followed by: Novartis and followed by: In total, each capsule is effective for about eight hours.

Quillivant XR is an extended-release oral suspension after reconstitution with water: It was designed and is patented and made by Pfizer. The medication comes in various sizes from 60ml to ml after reconstitution. The bottle must be shaken vigorously for ten seconds prior to administration via included oral syringe to ensure proper ratio.

Generic immediate-release methylphenidate is relatively inexpensive. Methylphenidate was first synthesized in , [] and was identified as a stimulant in Methylphenidate was synthesized by Ciba now Novartis chemist Leandro Panizzon. He named the drug after his wife, nicknamed Rita, who used Ritalin to compensate for low blood pressure.

Subsequent studies of the racemates showed that the central stimulant activity is associated with the threo racemate and were focused on the separation and interconversion of the erythro isomer into the more active threo isomer. Methylphenidate was first used to allay barbiturate -induced coma, narcolepsy and depression. Methylphenidate has been the subject of controversy in relation to its use in the treatment of ADHD.

The prescription of psychostimulant medication to children to reduce ADHD symptoms has been a major point of criticism. One of the highest use of methylphenidate medication is in Iceland, [ citation needed ] where research shows that the drug was the most commonly abused substance among intravenous substance abusers.

Treatment of ADHD by way of methylphenidate 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. In the US and the UK, it is approved for use in children and adolescents. Methylphenidate may have benefit as a treatment of apathy in patients with Alzheimer's disease.

From Wikipedia, the free encyclopedia. Not to be confused with Ethylphenidate. C Risk not ruled out. List of methylphenidate analogues. Methylphenidate preparation elucidated by Axten et al. Classic methylphenidate synthesis []. Another synthesis route of methylphenidate which applies Darzens reaction to obtain aldehyde as an intermediate.

This route is significant for its selectivity. National Center for Biotechnology Information. Retrieved 8 October Catecholamine Influences on Prefrontal Cortical Functions". Neuroscientific Basis and Practical Applications 4th ed. Journal of Clinical Psychopharmacology. Can J Clin Pharmacol. Archived from the original PDF on

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