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Methylphenidate, abbreviated MP or MPH, sold under the trade name Ritalin among others, is a stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is a first line medication for ADHD. It may be taken by mouth or applied to the skin, and different formulations have varying durations of effect. Common side effects of methylphenidate include difficulty sleeping, decreased appetite, anxiety, and weight loss. More serious side effects may include psychosis.

Methylphenidate , abbreviated MP or MPH , sold under the trade name Ritalin among others, is a stimulant medication used to treat attention deficit hyperactivity disorder ADHD and narcolepsy. Common side effects of methylphenidate include difficulty sleeping, decreased appetite, anxiety, and weight loss. Methylphenidate was first made in and was approved for medical use in the United States in Methylphenidate is most commonly used to treat ADHD and narcolepsy. Methylphenidate is used for the treatment of attention deficit hyperactivity disorder. The short-term benefits and cost effectiveness of methylphenidate are well established. Narcolepsy , a chronic sleep disorder characterized by overwhelming daytime drowsiness and uncontrollable sleep, is treated primarily with stimulants. Methylphenidate is considered effective in increasing wakefulness , vigilance, and performance. Methylphenidate may also be prescribed for off-label use in treatment-resistant cases of bipolar disorder and major depressive disorder. 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 Food and Drug Administration FDA gives methylphenidate a pregnancy category of C, and women are advised to only use the drug if the benefits outweigh the potential risks. 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 , and tachycardia rapid heart rate. There is some evidence of mild reductions in height with prolonged treatment in children. Hypersensitivity including skin rash , urticaria , and fever is sometimes reported when using transdermal methylphenidate. The Daytrana patch has a much higher rate of skin reactions than oral methylphenidate. Methylphenidate can worsen psychosis in people who are psychotic, 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. A Cochrane review found that methylphenidate might be associated with serious side effects such as heart problems, psychosis, and death; the certainty of the evidence was stated as very low and the actual risk might be higher. The symptoms of a moderate acute overdose on methylphenidate primarily arise from central nervous system overstimulation; these symptoms include: vomiting , nausea , agitation , tremors , hyperreflexia , muscle twitching, euphoria , confusion, hallucinations, delirium , hyperthermia , sweating, flushing , headache, tachycardia , heart palpitations , cardiac arrhythmias , hypertension , mydriasis , and dryness of mucous membranes. Methylphenidate is a stimulant with an addiction liability and dependence liability similar to amphetamine. It has moderate liability among addictive drugs ; \\\\\\\\\[73\\\\\\\\\] \\\\\\\\\[74\\\\\\\\\] 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 vitamin K 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 ethanol. 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 a psychostimulant and increases the activity of the central nervous system through inhibition on reuptake of the neurotransmitters norepinephrine and dopamine. When reuptake of those neurotransmitters is halted, its concentration and effects in the synapse increase and last longer, respectively. Therefore, methylphenidate is called a norepinephrine—dopamine reuptake inhibitor. 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 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. The dextrorotary enantiomers are significantly more potent than the levorotary enantiomers, and some medications therefore only contain dexmethylphenidate. 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 , enzymes in the liver. 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 mixture of erythro:threo diastereomers, but it was later reformulated to contain only the threo 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 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. Methylphenidate was first made 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. It is also sold in the majority of countries worldwide although in much lower volumes than in the United States. 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: '18', '27', '36', or '54', relating to the mg dosage strength. In total, each capsule is effective for about eight hours. 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. A methylphenidate skin patch is sold under the brand name Daytrana in the United States. It was developed and marketed by Noven Pharmaceuticals and approved in the US in It is also referred to as methylphenidate transdermal system MTS. It is approved as a once daily treatment in children — ages 6 to 17 — with ADHD. It is mainly prescribed as a second-line treatment when oral forms are not well tolerated or if people have difficulty with compliance. When the FDA rejected the submission they requested evidence that a shorter time period was safe and effective, Noven provided such evidence and it was approved for a 9-hour period. Orally administered methylphenidate is subject to first-pass metabolism , by which the levo- isomer is extensively metabolized. The absorption is increased when the transdermal patch is applied onto inflamed skin or skin that has been exposed to heat. The absorption lasts for approximately 9 hours after application onto normal, unexposed to heat and uninflamed skin. 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. Among countries with the highest rates of use of methylphenidate medication is Iceland, \\\\\\\\\[\\\\\\\\\] 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. From Wikipedia, the free encyclopedia. Medication of the stimulant class. IUPAC name. Interactive image. Top: this depicts the initial effects of high dose exposure to an addictive drug on gene expression in the nucleus accumbens for various Fos family proteins i. See also: List of methylphenidate analogues. Methylphenidate synthesis. Method 1: Methylphenidate preparation elucidated by Axten et al. Method 2: Classic methylphenidate synthesis \\\\\\\\\[\\\\\\\\\]. Method 3: Another synthesis route of methylphenidate which applies Darzens reaction to obtain aldehyde as an intermediate. This route is significant for its selectivity. Archived from the original on 19 December Retrieved 19 December Elsevier Health Sciences. Clinical Pharmacokinetics. Pubchem Compound. National Center for Biotechnology Information. Biological Psychiatry. Cambridge University Press. Academic Press. Pharmaceutical Journal. Retrieved 11 April Archived from the original on 31 January Retrieved 30 January Current Opinion in Pharmacology. Expert Rev Neurother. North Am. Pharmacoepidemiol Drug Saf. Is methylphenidate useful for treating adolescents with ADHD? The Journal of Family Practice. Archived from the original on 13 July Retrieved 30 April In Millichap, JG ed. New York: Springer. CNS Drugs. Our findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non-serious adverse events in children. Cochrane Database Syst Rev. Retrieved 26 March Archived from the original on 13 November Retrieved 12 November Child Adolesc. J Clin Psychiatry. A Meta-analytic Review of the Literature'. Harm Reduction Journal. Expert Review of Neurotherapeutics. Handbook of adolescent health care. Curr Psychiatry Rep. Hum Psychopharmacol. The Cochrane Database of Systematic Reviews. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Collectively, this evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers improving PFC-dependent function. Archived from the original on 19 September Retrieved 14 November Specifically, in a set of experiments limited to high-quality designs, we found significant enhancement of several cognitive abilities. The results of this meta-analysis Therapeutic relatively low doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in normal subjects and those with ADHD. Positron emission tomography PET demonstrates that methylphenidate decreases regional cerebral blood flow in the doroslateral prefrontal cortex and posterior parietal cortex while improving performance of a spatial working memory task. This suggests that cortical networks that normally process spatial working memory become more efficient in response to the drug. At abused relatively high doses, stimulants can interfere with working memory and cognitive control Thus, stimulants improve performance on effortful but tedious tasks JS Online. Archived from the original on 15 August Retrieved 2 December Sports Med. United States Food and Drug Administration. Archived PDF from the original on 23 June Retrieved 23 June Noven Pharmaceuticals, Inc. October Archived PDF from the original on 14 July Retrieved 13 June Archived from the original on 2 January Canadian Family Physician. Pharmaceutical Research. Archived from the original PDF on 20 July Optometry Clinics. March Archives of Disease in Childhood. Wiley Interdisciplinary Reviews. Cognitive Science. Clinical Neuropharmacology. Psychopharmacology Bulletin. Food and Drug Administration. Archived from the original on 17 December Retrieved 17 December Archived from the original on 30 October Retrieved 4 November International Journal of Clinical Practice. May International Programme on Chemical Safety. Archived from the original on 23 June The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Swiss Med Wkly. Bibcode : PNAS Clinical Psychopharmacology and Neuroscience. Cocaine, \\\\\\\\\[amphetamine\\\\\\\\\], and methamphetamine are the major psychostimulants of abuse. The related drug methylphenidate is also abused, although it is far less potent. Such agents also have important therapeutic uses; cocaine, for example, is used as a local anesthetic Chapter 2 , and amphetamines and methylphenidate are used in low doses to treat attention deficit hyperactivity disorder and in higher doses to treat narcolepsy Chapter Despite their clinical uses, these drugs are strongly reinforcing, and their long-term use at high doses is linked with potential addiction, especially when they are rapidly administered or when high-potency forms are given. Bibcode : PNAS.. Despite decades of clinical use of methylphenidate for ADHD, concerns have been raised that long-term treatment of children with this medication may result in subsequent drug abuse and addiction. However, meta analysis of available data suggests that treatment of ADHD with stimulant drugs may have a significant protective effect, reducing the risk for addictive substance use 36, Studies with juvenile rats have also indicated that repeated exposure to methylphenidate does not necessarily lead to enhanced drug-seeking behavior in adulthood However, the recent increase of methylphenidate use as a cognitive enhancer by the general public has again raised concerns because of its potential for abuse and addiction 3, 6— Thus, although oral administration of clinical doses of methylphenidate is not associated with euphoria or with abuse problems, nontherapeutic use of high doses or i. Substance Abuse. Journal of Clinical Psychopharmacology. Archived from the original on 1 July Retrieved 1 July The International Journal of Neuropsychopharmacology. Archived from the original PDF on 15 December Drug and Alcohol Review. Dialogues in Clinical Neuroscience. Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process : the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict. Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure 60,95,97, Some of these proposed interventions have limitations or are in their infancy However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction. Annals of Agricultural and Environmental Medicine. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. Nature Reviews. Janssen Pharmaceuticals. Archived PDF from the original on 28 January Retrieved 4 December Psychiatry and Clinical Neurosciences. Expert Opinion on Drug Delivery. Drug Metabolism and Disposition. Clinical Pharmacology and Therapeutics. Drug Metab. Behavioural Pharmacology. Journal of Child and Adolescent Psychopharmacology. Can J Clin Pharmacol. British Journal of Pharmacology. Journal of Attention Disorders. JAMA Psychiatry. September The Journal of Clinical Psychiatry. Acta Psychiatrica Scandinavica. Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure. Neural Plasticity. Archived from the original PDF on 14 July Archived from the original on 17 October Journal of Neurochemistry. Basal Ganglia. Despite the challenges in determining synaptic vesicle pH, the proton gradient across the vesicle membrane is of fundamental importance for its function. Exposure of isolated catecholamine vesicles to protonophores collapses the pH gradient and rapidly redistributes transmitter from inside to outside the vesicle. Amphetamine and its derivatives like methamphetamine are weak base compounds that are the only widely used class of drugs known to elicit transmitter release by a non-exocytic mechanism. As substrates for both DAT and VMAT, amphetamines can be taken up to the cytosol and then sequestered in vesicles, where they act to collapse the vesicular pH gradient. Die Pharmazie. Current Neuropharmacology. Archived from the original on 29 September Retrieved 11 March Archived PDF from the original on 10 February Effects on plasma concentration of methylphenidate and ritalinic acid'. August The Journal of Pharmacology and Experimental Therapeutics. The Journal of Organic Chemistry. Chemical Reviews. Helvetica Chimica Acta. Klinische Wochenschrift. Archived from the original on 2 February Retrieved 24 September The most important chemical compounds: a reference guide. Retrieved 10 September Encyclopedia of psychopharmacology. Berlin London: Springer. Archived from the original PDF on 24 August Retrieved 22 July Archived from the original on 12 October Retrieved 2 November World Health Organization. Retrieved 16 November January Retrieved 18 June Journal of Clinical Pharmacology. Archived from the original on 26 March Illinois DocAssist website. University of Illinois at Chicago. Archived from the original on 1 January Retrieved 26 July Apotex Inc. Sandoz Canada Inc. Archived PDF from the original on 3 December US Food and Drug Administration. Archived from the original on 2 October Retrieved 1 October Archived PDF from the original on 2 February Retrieved 15 April Family Practice Notebook. Archived from the original on 14 September Retrieved 7 August Archived from the original on 11 June Retrieved 11 June Archived from the original on 16 April Retrieved 16 April Archived from the original on 7 January Archived from the original on 10 July Quillivant PI Sheet. Archived from the original on 18 October Retrieved 13 October Scott Archived from the original PDF on 1 August Drug prices in the US are often higher than in Canada. The GoodRx website correctly points out that short-term refills e. However, if a patient ignores the coupons, and if the patient does not shop around, the website indicates that it is possible to pay more than twelve US dollars per defined daily dose. Data retrieved 17 May Archived from the original PDF on 31 August Retrieved 2 March Office of Public Sector Information. Retrieved 15 June Archived from the original on 3 April Retrieved 26 April Therapeutic Goods Administration. Retrieved 28 June Retrieved 17 October Ministry of Justice. Archived from the original on 6 October Retrieved 15 January Br J Clin Pharmacol. Government of India. Archived from the original on 8 August Retrieved 5 December Ministry of Home Affairs, Government of India. Archived PDF from the original on 5 March Clin Pract Epidemiol Ment Health. Archived from the original on 28 May European Journal of Clinical Pharmacology. Journal of Addiction Medicine. Journal of Child Neurology. Journal of Geriatric Psychiatry and Neurology. Obesity Research. Adapromine Amantadine Bromantane Memantine Rimantadine. Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide. ATC code : N06B. ADHD pharmacotherapies. Amphetamine Mixed amphetamine salts , Levoamphetamine , Dextroamphetamine , Lisdexamfetamine Methamphetamine Methylphenidate Dexmethylphenidate. Armodafinil Atomoxetine Modafinil. Clonidine Guanfacine. Amantadine Carbamazepine. Recreational drug use. Calea zacatechichi Silene capensis. Coffee break Coffeehouse Latte art Tea house. Abuse Date rape drug Impaired driving Drug harmfulness Effects of cannabis Addiction Dependence Prevention Opioid replacement therapy Rehabilitation Responsible use Drug-related crime Fetal alcohol spectrum disorder Long-term effects of cannabis Neurotoxicity Overdose Passive smoking of tobacco or other substances. Arguments for and against drug prohibition Capital punishment for drug trafficking Cognitive liberty Designer drug Drug court Drug possession Drug test Narc Politics of drug abuse War on drugs Mexican drug war Plan Colombia Philippine drug war Zero tolerance. Alcohol legality Alcohol consumption Anabolic steroid legality Cannabis legality Annual use Lifetime use Cigarette consumption Cocaine legality Cocaine use Methamphetamine legality Opiates use Psilocybin mushrooms legality Salvia legality. Monoamine reuptake inhibitors. Others: Antihistamines e. Others: A Amoxapine Antihistamines e. Amiodarone Amphetamines e. Sigma receptor modulators. Medicine portal. Hidden categories: CS1: long volume value All articles with dead external links Articles with dead external links from April Articles with permanently dead external links Webarchive template wayback links Articles with short description Short description is different from Wikidata Use dmy dates from May ECHA InfoCard ID from Wikidata Infobox drug articles with non-default infobox title Drugboxes which contain changes to watched fields Wikipedia articles needing factual verification from June Commons category link is on Wikidata Wikipedia medicine articles ready to translate. Namespaces Article Talk. Views Read Edit View history. Help Learn to edit Community portal Recent changes Upload file. Download as PDF Printable version. Wikimedia Commons. High \\\\\\\\\[1\\\\\\\\\]. By mouth , transdermal \\\\\\\\\[1\\\\\\\\\]. CNS stimulant. Currently unavailable. XR capsule. OROS tablet. ER capsule. CR tablet. Wikimedia Commons has media related to Methylphenidate.

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