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It is a primary medication for ADHD e. Common adverse reactions of methylphenidate include euphoria , dilated pupils , tachycardia , palpitations , headache , insomnia , anxiety , hyperhidrosis , weight loss , decreased appetite , dry mouth , nausea , and abdominal pain. Methylphenidate is believed to work by blocking the reuptake of dopamine and norepinephrine by neurons. It is available as a generic medication. The word methylphenidate is a portmanteau of the chemical name, Methyl phen yl p i peri d inyl acet ate. The name 'Ritalin' derives from Marguerite 'Rita' Panizzon, the wife of Leandro Panizzon, who first synthesized the drug in Rita was the first person to take methylphenidate, and described its effects to her husband. Methylphenidate is most commonly used to treat ADHD and narcolepsy. Methylphenidate is used for the treatment of attention deficit hyperactivity disorder ADHD. The International Consensus Statement on ADHD shows that the results from systematic reviews , meta-analyses and large scale studies are clear: methylphenidate is safe and efficacious, but also among the most efficacious drugs in all of medicine; treatment in the long-term significantly reduces or eliminates the elevated risks for obesity, accidental injuries, traumatic brain injury, substance abuse, cigarette smoking, educational underachievement, bone fractures, sexually transmitted infections, depression, suicide, criminal activity, teenage pregnancy, vehicle crashes, burn injuries and overall-cause mortality. One committee from the World Health Organization WHO responsible for the World Health Organization Essential Medicines List rejected an application in , and a second application endorsed by 51 professional medical groups in , for methylphenidate's inclusion due to uncertainty about its efficacy and safety. Safety and efficacy data have been reviewed extensively by medical regulators e. These professional groups unanimously conclude, based on the scientific evidence, that methylphenidate is safe and effective and should be considered as a first-line treatment for ADHD. Since ADHD diagnosis has increased around the world, methylphenidate may be misused as a 'study drug' by some populations, which may be harmful. Long-term meta-analyses and systematic reviews show that the medications used to treat ADHD are not associated with observed deficits in brain structure, but with improved brain development and functioning, most prominently in inferior frontal and striatal regions. 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. Methylphenidate's efficacy as an athletic performance enhancer , cognitive enhancer , aphrodisiac , and euphoriant is supported by research. Excessive doses of methylphenidate, above the therapeutic range, can interfere with working memory and cognitive control. Methylphenidate is contraindicated for individuals with agitation, tics , glaucoma , heart defects or a hypersensitivity to any ingredients contained in methylphenidate pharmaceuticals. Pregnant women are advised to only use the medication if the benefits outweigh the potential risks. Cardiac adverse effects may include palpitations , changes in blood pressure , and heart rate typically mild , and tachycardia rapid heart rate. Results from a systematic review showed that methylphenidate significantly improves ADHD symptoms and broadband measures but can cause appetite suppression and other adverse events in children and adolescents. 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. Food and Drug Administration-commissioned studies in 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. The same review found tentative evidence that it may cause both serious and non-serious adverse effects in children. 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 ; \[ \] \[ \] accordingly, addiction and psychological dependence are possible and likely when methylphenidate is used at high doses as a recreational drug. Methylphenidate has the potential to induce euphoria due to its pharmacodynamic effect i. At therapeutic doses, ADHD stimulants do not sufficiently activate the reward system; consequently, when taken as directed in doses that are commonly prescribed for the treatment of ADHD, methylphenidate use lacks the capacity to cause an addiction. 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 , \[ \] \[ \] 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 acts primarily as a strong 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. As models of ADHD suggest, it is associated with functional impairments in some of the brain's neurotransmitter systems , particularly those involving dopamine in the mesocortical and mesolimbic pathways and norepinephrine in the prefrontal cortex and locus coeruleus. 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 NE. 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. There exist some paradoxical findings that oppose the notion that methylphenidate acts as silent antagonist of the DAT DAT inhibitor. Methylphenidate may protect neurons from the neurotoxic effects of Parkinson's disease and methamphetamine use disorder. The dextrorotary enantiomers are significantly more potent than the levorotary enantiomers, and some medications therefore only contain dexmethylphenidate. Ritalin , 3—8 hours for sustained-release i. Ritalin SR , and 8—12 hours for extended-release i. The half-life of methylphenidate is 2—3 hours, depending on the individual. The peak plasma time is achieved at about 2 hours. Dextromethylphenidate is much more bioavailable than levomethylphenidate when administered orally, and is primarily responsible for the psychoactivity of racemic methylphenidate. The oral bioavailability and speed of absorption for immediate-release methylphenidate is increased when administered with a meal. Methylphenidate is metabolized into ritalinic acid by CES1A1 enzymes in the liver. Dextromethylphenidate is selectively metabolized at a slower rate than levomethylphenidate. Despite the claim made by some urban legends, it is not a cocaine derivative nor analog, however both compounds contain a methyl piperidinylcarboxylate moiety with 2- carbon distance between nitrogen and methanoate , methylphenidate containing methyl piperidinyl -ethanoate and cocaine containing methyl piperidinyl -methanoate. 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 synthesized in and was approved for medical use in the United States in Methylphenidate was first used to allay barbiturate -induced coma, narcolepsy and depression. Methylphenidate is sold in the majority of countries worldwide. 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. There is some evidence that dexmethylphenidate has better bioavailability and a longer duration of action than methylphenidate. Methylphenidate was originally available as an immediate-release racemic mixture formulation under the Novartis brand name Ritalin, although a variety of generics are 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 dosage strength in milligrams. Ritalin LA \[ 85 \] provides two standard doses — half the total dose being released immediately and the other half released four hours later. In total, each capsule is effective for about eight hours. Jornay PM is a delayed release formulation that is taken at bedtime. An outer polymer coating delays the initial release of the drug until 8 hours after administration, after which an inner coating regulates the rate of drug absorption. Peak plasma concentration occurs 14 hours following administration. 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 approved as a once-daily treatment in children with ADHD aged 6—17 years. It is mainly prescribed as a second-line treatment when oral forms are not well tolerated, or if people have difficulty with compliance. Noven's original FDA submission indicated that it should be used for 12 hours. 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. When it was released in the United States, methylphenidate was available from CIBA in a parenteral form for use by medical professionals. It came in 10mL multiple-dose vials containing mg methylphenidate HCl and mg lactose in lyophilized freeze-dried form. It was also available as single-dose ampoules containing 20 mg methylphenidate HCl. Instructions were to reconstitute with 10mL sterile solvent water. The indication was 10 to 20 mg 1. Parenteral methylphenidate was discontinued out of a concern for the actual benefit and of inducing a psychic dependence. This is not truth serum in the normal sense, as it does not impair the ability to control the flow of information like a barbiturate agent Pentothal or similar might. Brand-name and generic formulations are available. 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 used substance among people who inject drugs. 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. Methylphenidate may be effective as a treatment for apathy in Alzheimer's disease and other conditions. Methylphenidate has shown some benefits as a replacement therapy for individuals who are addicted to and dependent upon methamphetamine. Methylphenidate has been reported to be effective in the treatment of social anxiety disorder in people who are comorbid for both this condition and attention deficit hyperactivity disorder ADHD in small preliminary clinical studies and case reports. Stimulants: Phenylethanolamine. Contents move to sidebar hide. Article Talk. Read Edit View history. Tools Tools. Download as PDF Printable version. In other projects. Wikimedia Commons. Central nervous system stimulant. Not to be confused with Ryetalyn. US DailyMed : Methylphenidate. Instant-release: 3—4 hours Extended-release: 6—12 hours. IUPAC name. DB Y. D Y. Interactive image. Etymology \[ edit \]. Uses \[ edit \]. Attention deficit hyperactivity disorder \[ edit \]. Narcolepsy \[ edit \]. Other medical uses \[ edit \]. Enhancing performance \[ edit \]. Contraindications \[ edit \]. Adverse effects \[ edit \]. Overdose \[ edit \]. Addiction and dependence \[ edit \]. Biomolecular mechanisms \[ edit \]. Interactions \[ edit \]. Pharmacology \[ edit \]. Pharmacodynamics \[ edit \]. Pharmacokinetics \[ edit \]. Chemistry \[ edit \]. See also: List of methylphenidate analogues. Methylphenidate synthesis. Method 1: Methylphenidate preparation elucidated by Axten et al. Method 2: Classic methylphenidate synthesis \[ \]. Detection in biological fluids \[ edit \]. History \[ edit \]. Society and culture \[ edit \]. Names \[ edit \]. Available forms \[ edit \]. Immediate-release \[ edit \]. Structural formula for the substance among Ritalin tablet series. The volume of distribution was 2. Structural formula for the substance inside Concerta tablet. Extended-release \[ edit \]. Skin patch \[ edit \]. Parenteral formulation \[ edit \]. Cost \[ edit \]. Legal status \[ edit \]. Controlled Substance. Controversy \[ edit \]. Research \[ edit \]. Apathy \[ edit \]. Addiction \[ edit \]. Social anxiety \[ edit \]. Footnotes \[ edit \]. At abused relatively high doses, stimulants can interfere with working memory and cognitive control Thus, stimulants improve performance on effortful but tedious tasks 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. However, fatalities are rare with appropriate care. 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. 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. References \[ edit \]. PMC PMID Archived from the original on 19 December Retrieved 19 December Today's Medical Assistant: Clinical and administrative procedures. Elsevier Health Sciences. ISBN Archived from the original on 28 July Retrieved 20 August Retrieved 22 October Archived from the original on 3 August Retrieved 3 August Health Canada. Archived from the original on 11 June Retrieved 11 June Justice Laws Website. 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Psychiatry and Clinical Neurosciences. Expert Opinion on Drug Delivery. June Drug Metabolism and Disposition. Clinical Pharmacology and Therapeutics. Drug Metabolism Reviews. Behavioural Pharmacology. The Canadian Journal of Clinical Pharmacology. Archived from the original PDF on 15 December JAMA Psychiatry. The Journal of Clinical Psychiatry. Acta Psychiatrica Scandinavica. Neural Plasticity. Archived from the original on 6 August Retrieved 5 February Archived from the original on 17 October Journal of Neurochemistry. Annals of the New York Academy of Sciences. Basal Ganglia. Die Pharmazie. Bibcode : PNAS Drug and Alcohol Dependence. Archived from the original on 29 September Retrieved 11 March Effects on plasma concentration of methylphenidate and ritalinic acid'. Retrieved 12 December Retrieved 25 May Retrieved 26 May The Journal of Pharmacology and Experimental Therapeutics. Neuropathology of Drug Addictions and Substance Misuse. Academic Press. Archived from the original on 29 August The Journal of Organic Chemistry. Chemical Reviews. Disposition of Toxic Drugs and Chemicals in Man 9th ed. Attention Deficit and Hyperactivity Disorders. ACS Chem Neurosci. Helvetica Chimica Acta. Archived from the original on 2 February Retrieved 24 September — via Google Books. Klinische Wochenschrift in German. Pharmacol Rev. Retrieved 10 September Encyclopedia of Psychopharmacology. Archived from the original PDF on 24 August Retrieved 22 July Drug Enforcement Administration. Archived from the original on 12 October Retrieved 2 November Archived from the original on 27 March Archived from the original on 16 December Retrieved 30 April The Pharmaceutical Journal. Royal Pharmaceutical Society. Application for inclusion to the 22nd expert committee on the selection and use of essential medicines: Methylphenidate hydrochloride PDF Report. World Health Organization. Archived PDF from the original on 6 August Retrieved 16 November Product Monograph. Pickering, Ontario, Canada: Purdue Pharma. Submission Control Nr Retrieved 14 December — via caddra. Illinois DocAssist. Clinical resources. Chicago, IL: University of Illinois. Archived from the original on 1 January Retrieved 26 July Apotex Inc. Sandoz Canada Inc. Archived PDF from the original on 3 December Drugs FDA. 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 Pfizer Medical Information pfizermedicalinformation. Archived from the original on 16 April Retrieved 16 April Retrieved 27 April Archived from the original on 7 January Drug information: User reviews, side effects, drug interactions, and dosage. Archived from the original on 10 July Retrieved 9 January J Child Adolesc Psychopharmacol. Noven Pharmaceuticals. NDA No. Archived from the original PDF on 30 September Retrieved 17 January — via U. Food and Drug Administration. Archived from the original PDF on 31 August Retrieved 2 March Therapeutic Goods Administration. Archived from the original on 1 July Retrieved 28 June Department of Justice, Government of Canada. Archived from the original on 3 April Retrieved 26 April Archived from the original PDF on 13 July Retrieved 5 August Hong Kong e-Legislation. Archived from the original on 28 August Retrieved 20 March Government of India. Archived from the original on 8 August Retrieved 5 December Archived from the original PDF on 5 March Archived PDF from the original on 26 March Retrieved 17 October Ministry of Justice. Archived from the original on 6 October Retrieved 15 January Misuse of Drugs Act c. Office of Public Sector Information. Retrieved 15 June Isomer Design. Bureau of Narcotics and Dangerous Drugs. Archived PDF from the original on 3 March Retrieved 16 January Clinical Practice and Epidemiology in Mental Health. Archived from the original on 28 May A meta-analytic review of the literature'. European Journal of Clinical Pharmacology. Journal of Addiction Medicine. Journal of Child Neurology. Cochrane Database Syst Rev. Psychopharmacology Berl. Journal of Geriatric Psychiatry and Neurology. Current Psychiatry. Neurosci Biobehav Rev. Substance Abuse. Retrieved 11 February Drug and Alcohol Review. Int Clin Psychopharmacol. Drugs Context. Expert Rev Neurother. Koyuncu et al. The impact of this association on response to treatment still needs investigations, but preliminary studies showed that atomoxetine and methylphenidate can be effective in treating both ADHD and comorbid SAD \[99,\]. J Psychiatr Pract. Ther Adv Psychopharmacol. External links \[ edit \]. Wikimedia Commons has media related to Methylphenidate. Adapromine Amantadine Bromantane Memantine Rimantadine. Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide. ATC code : N06B. ADHD pharmacotherapies. Armodafinil Atomoxetine Modafinil Viloxazine. Clonidine Guanfacine. Amantadine Carbamazepine. Recreational drug use. Calea zacatechichi Silene capensis. Drug culture. Coffee break Coffeehouse Latte art Teahouse. Alcohol legality Anabolic steroid legality Cannabis legality Cocaine legality Methamphetamine legality Psilocybin decriminalization in the U. Psilocybin mushrooms legality Salvia legality. Arguments for and against drug prohibition Cannabis rights 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. 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Such drugs must be kept in a lockable safe until dispensed and possession without prescription is punishable by fines and imprisonment. Unlawful possession for the purpose of trafficking is punishable by up to ten years imprisonment, or via summary conviction by up to eighteen months imprisonment. Covered by the 'narcotics' schedule, prescription and distribution conditions are restricted, with hospital or city specialist-only pediatrician for children, psychiatrist or neurologist for adults prescription for the initial treatment and yearly consultations. Hong Kong. Methylphenidate is a schedule X drug and is controlled by the Drugs and Cosmetics Rules, It is dispensed only by physician's prescription. Legally, 2 grams of methylphenidate is classified as a small quantity, and 50 grams as a large or commercial quantity. New Zealand. In New Zealand, methylphenidate is a 'class B2 controlled substance'. Unlawful possession is punishable by six-month prison sentence and distribution by a year sentence. List I controlled psychotropic substance without recognized medical value. List II controlled substance with recognized medical value. Possession without a prescription is punishable by up to three years in prison. United Kingdom. Controlled 'Class B' substance. Possession without prescription carries a sentence up to 5 years or an unlimited fine, or both; supplying methylphenidate is 14 years or an unlimited fine, or both. United States. Classified as a Schedule II controlled substance , the designation used for substances that have a recognized medical value but present a high potential for misuse. Germany United States Israel.

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