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Метилфенидат гидрохлорид

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. 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 sometimes used by students to enhance their mental abilities, improving their concentration and helping them to study. John Harris , an expert in bioethics , has said that it would be unethical to stop healthy people taking the drug. He pointed out the logical non sequitur which would result if people were to draw a parallel between the claims of a university that they could 'set out deliberately to improve the mental capacities of its students; suppose its stated aims were to ensure that students left the university more intelligent and learned than when they arrived. Suppose they further claimed that not only could they achieve this but that their students would be more intelligent and mentally alert than any students in history. Barbara Sahakian has argued that the use of Ritalin in this way may give students an unfair advantage in examinations and that as a result universities may want to discuss making students give urine samples to be tested for the drug. 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. 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 ; \\\\\\\\\\\\\\\\\[76\\\\\\\\\\\\\\\\\] \\\\\\\\\\\\\\\\\[77\\\\\\\\\\\\\\\\\] 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 , \\\\\\\\\\\\\\\\\[93\\\\\\\\\\\\\\\\\] \\\\\\\\\\\\\\\\\[94\\\\\\\\\\\\\\\\\] 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 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. 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. 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 \\\\\\\\\\\\\\\\\[\\\\\\\\\\\\\\\\\]. 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 Is methylphenidate useful for treating adolescents with ADHD? The Journal of Family Practice. Archived from the original on 13 July Retrieved 30 April Expert Review of Neurotherapeutics. 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. Attention Deficit Hyperactivity Disorder Handbook: Cochrane Database Syst Rev. Current Opinion in Pharmacology. Monoamines, Acetylcholine, and Orexin'. A Foundation for Clinical Neuroscience 2nd ed. Retrieved 12 November A Meta-analytic Review of the Literature'. 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. 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 Higher Cognitive Function and Behavioral Control'. 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 Archived from the original on 15 August Retrieved 2 December United States Food and Drug Administration. Retrieved 23 June Retrieved 21 February Retrieved 13 June Retrieved on 30 April European journal of clinical pharmacology. Retrieved 22 June Archived from the original PDF on 22 June Retrieved 4 December Journal of Learning Disabilities. Food and Drug Administration. Retrieved 17 December Retrieved 4 November International Programme on Chemical Safety. 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. Reinforcement and Addictive Disorders'. 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. 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. Archived from the original PDF on 15 December Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: 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. Am J Drug Alcohol Abuse. 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. 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. Psychiatry and clinical neurosciences. Expert Opinion on Drug Delivery. Drug Metabolism and Disposition. Clinical Pharmacology and Therapeutics. Journal of child and adolescent psychopharmacology. British Journal of Pharmacology. Journal of Attention Disorders. 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. J 14 February Effects on plasma concentration of methylphenidate and ritalinic acid'. The Journal of Pharmacology and Experimental Therapeutics. Preparation and Biological Evaluation of Novel Analogues'. The Journal of Organic Chemistry. The Journal of Clinical Pharmacology. University of Illinois at Chicago. Retrieved 26 July US Food and Drug Administration. Retrieved 1 October Retrieved 15 April Retrieved 7 August Retrieved 11 June Retrieved 16 April Retrieved 13 October International Drug Price Indicator Guide. Retrieved 9 May Drug prices in the US are often higher than in Canada. The GoodRx website correctly points out that short-term refills e. For 30 tablets of brand-name Concerta 27 mg, the relevant GoodRx webpage offers coupons. 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 The Most Important Chemical Compounds: Patent 2,, Issue date: The most important chemical compounds: Retrieved 10 September History of its Use, Effects and Side Effects. Archived from the original PDF on 24 August Archived from the original on 12 October Retrieved 2 November Annex to the annual statistical report on psychotropic substances form P ' PDF. Archived from the original PDF on 31 August Retrieved 2 March Office of Public Sector Information. Retrieved 15 June Retrieved 28 June Retrieved 15 January British Journal of Clinical Pharmacology. Retrieved 5 December Ministry of Home Affairs, Government of India. Clin Pract Epidemol Ment Health. A Descriptive Population-Based Study'. Journal of Addiction Medicine. Journal of Child Neurology. Retrieved on 5 December Journal of Geriatric Psychiatry and Neurology. Adapromine Amantadine Bromantane Memantine Rimantadine. Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide. 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. 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. Selective norepinephrine reuptake inhibitors: Amoxapine Maprotiline Mianserin Oxaprotiline Setiptiline. Selective serotonin reuptake inhibitors: A Amoxapine Antihistamines e. Retrieved from ' https: Biology of bipolar disorder Carboxylate esters Euphoriants Methyl esters Methylphenidate Nootropics Norepinephrine-dopamine reuptake inhibitors Piperidines Sigma agonists Stimulants Treatment and management of attention deficit hyperactivity disorder Vasoconstrictors Phenethylamines Ergogenic aids World Anti-Doping Agency prohibited substances. Views Read Edit View history. In other projects Wikimedia Commons. This page was last edited on 10 September , at By using this site, you agree to the Terms of Use and Privacy Policy. By mouth , insufflation, intravenous, transdermal. Wikimedia Commons has media related to Methylphenidate.

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