Methylphenidate 205878 224852185 2008-07-10T18:27:50Z 38.117.134.222 /* History */ {{redirect|Vitamin R|the Chevelle song|Vitamin R (Leading Us Along)}} {{drugbox | IUPAC_name = methyl 2-phenyl-2-(piperidin-2-yl) acetate | image = Methylphenidate-2D-skeletal.svg | width = 175 | CAS_number = 113-45-1 | ATC_prefix = N06 | ATC_suffix = BA04 | ATC_supplemental = | PubChem = 4158 | DrugBank = APRD00657 | C=14 | H=19 | N=1 | O=2 | molecular_weight = 233.31 g/mol | smiles = COC(=O)C(C1CCCCN1)c1ccccc1 | bioavailability = 11&ndash;52% | protein_bound = 30% | metabolism = [[Liver]] | elimination_half-life = 2&ndash;4 hours | pregnancy_category = C | legal_AU = Schedule 8 | legal_CA = Schedule III | legal_UK = Class B | legal_US = Schedule II | legal_status = | routes_of_administration = Oral, Transdermal, IV, Nasal | excretion = [[Urine]] }} {| border="1" cellpadding="3" cellspacing="0" align="right" width="250px" style="border-collapse: collapse; margin: 0 0 0 0.5em" |- </table><table bgcolor="#ffffff" border="1" cellpadding="3" cellspacing="0" align="right" width="167px" style="border-collapse: collapse; clear: right; margin: 0 0 0 0.5em"> |- |'''Indicated for:'''<br /> *[[attention deficit disorder|ADD]] *[[attention deficit hyperactivity disorder|ADHD]] *[[narcolepsy]] '''Other uses:'''<br /> *[[treatment-resistant depression]] *[[appetite suppressant]] *[[antidepressant]] augmentation |- |'''[[Contraindication]]s:'''<br /> * Use of [[tricyclic antidepressant]]s (e.g. [[desipramine]]), as methylphenidate may dangerously increase their plasma concentrations, leading to potential toxic reactions (mainly, cardiovascular effects). * Use of MAO Inhibitors, such as phenelzine (Nardil) or tranylcypromine (Parnate), and certain other drugs. * methylphenidate should not be given to patients who suffer from the following conditions: Severe [[Arrhythmia]], [[Arterial hypertension|Hypertension]] or [[Liver|Liver damage]]. * Drug-seeking behaviour * Pronounced agitation or nervousness. Other side effects include drowsiness, and mood swings |- |'''[[Adverse drug reaction|Side effects]]:'''<ref>{{cite web|title= Methylphenidate - Oral (Ritalin) side effects, medical uses and drug interactions|url= http://www.medicinenet.com/methylphenidate-oral/page2.htm#SideEffects| accessdate=2007-11-02}}</ref><ref>{{cite web|title=Ritalin (methylphenidate) Side Effects and Abuse|url=http://www.add-adhd-help-center.com/ritalin_side_effects.htm|accessdate=2007-11-02}}</ref> '''''Atypical [[sensation]]s:''''' * '''''[[Cardiovascular]]:''''' * [[Arrhythmia]] or * increase in blood pressure '''''[[Ear]], [[nose]], and [[throat]]:''''' * '''''[[Endocrinal]]:''''' * Appetite loss '''''[[Eye]]:''''' * Blurred vision '''''[[Gastrointestinal]]:''''' * Nausea/vomiting, abdominal pain '''''[[Hematological]]:''''' * '''''[[Muscle|Musculo]][[skeletal]]:''''' * Muscle twitches '''''[[Neurological]]:''''' * [[Insomnia]], drowsiness, [[dizziness]], [[headache]] '''''[[Psychological]]:''''' * [[Psychosis]] (abnormal thoughts or hallucinations) * [[Nervousness]] * [[Euphoria (emotion)|Euphoria]] '''''[[Respiration (physiology)|Respiratory]]:''''' * Increased respiration rate '''''[[Skin]]:''''' * '''''[[Urogenital]] and [[reproductive]]:''''' * '''''Miscellaneous:''''' *Fever |} '''Methylphenidate''' ('''MPH''') is a [[medical prescription|prescription]] [[stimulant]] commonly used to treat [[Attention-deficit hyperactivity disorder]], or ADHD. It is also one of the primary [[drug]]s used to treat the daytime [[drowsiness]] symptoms of [[narcolepsy]] and [[chronic fatigue syndrome]]. The drug is seeing early use to treat cancer-related fatigue.<ref>{{cite news |title=An Old Drug May Give Cancer Patients a Lift |url=http://www.cancer.org/docroot/NWS/content/NWS_1_1x_An_Old_Drug_May_Give_Cancer_Patients_a_Lift.asp |work=ACS News Center |publisher=American Cancer Society |date=2002-01-24 |accessdate=2008-02-24 }}</ref> Brand names of drugs that contain methylphenidate include '''Ritalin''' ('''Ritalina''', '''Rilatine''', '''Attenta''', '''Methylin''', '''Penid''', '''Rubifen'''); and the [[sustained release]] tablets '''Concerta''', '''Metadate CD''', '''Methylin ER''', '''Ritalin LA''', and '''Ritalin-SR'''. '''Focalin''' is a preparation containing only [[dexmethylphenidate|dextro-methylphenidate]], rather than the usual [[racemic]] dextro- and levo-methylphenidate mixture of other formulations. A newer way of taking methylphenidate is by using a [[transdermal patch]] (under the brand name [[Daytrana|'''Daytrana''']]), similar to those used for hormone replacement therapy, nicotine release and pain relief ([[fentanyl]]). == History == Methylphenidate (or ritalin) was patented in 1954 by the CIBA pharmaceutical company (now [[Novartis]]) as a potential cure for [[Mohr's disease]].{{Fact|date=July 2008}} 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 most commonly prescribed medication to treat ADHD around the world.{{Fact|date=May 2008}} 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.<ref>{{cite web|url=http://www.dea.gov/pubs/cngrtest/ct051600.htm|title=News from DEA, Congressional Testimony, 05/16/00|accessdate=2007-11-02}}</ref> Most brand-name Ritalin is produced in the [[United States]], and methylphenidate is produced in the United States, [[Mexico]], [[Argentina]] and [[Pakistan]]. Other generic forms, such as "methylin", are produced by several U.S. pharmaceutical companies. Ritalin is also sold in the [[United Kingdom]], [[Germany]] and other European countries (although in much lower volumes than in the United States). These generic versions of methylphenidate tend to outsell brand-name Ritalin four to one.{{Fact|date=May 2008}} In Belgium the product is sold under the name "Rilatine". 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.<ref name="steele">Steele, M., ''et al.'' (2006). "{{PDFlink|[http://www.cjcp.ca/pdf/CJCP_05-012_e50.pdf A randomized, controlled effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in Attention Deficit-Hyperactivity Disorder]|293&nbsp;KB}}". ''Can J Clin Pharmacol''. 2006 Winter;13(1):e50-62.</ref><ref>Pelham, W.E., ''et al.'' (2001). "[http://pediatrics.aappublications.org/cgi/content/full/107/6/e105 Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings]". ''Pediatrics''. 2001 Jun;107(6):E105.</ref><ref>Keating, G.M., McClellan, K., Jarvis, B. (2001). "[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11524026&query_hl=77&itool=pubmed_docsum Methylphenidate (OROS formulation)]". ''CNS Drugs''. 2001;15(6):495-500; discussion 501-3.</ref><ref> Hoare, P., ''et al.'' (2005). "{{PDFlink|[http://www.springerlink.com/media/2g540pxwql2vyrnntdtx/contributions/k/7/3/3/k733x1l613771565.pdf 12-month efficacy and safety of OROS methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder switched from MPH]}}". ''Eur Child Adolesc Psychiatry''. 2005 Sep;14(6):305-9.</ref> Time-release medications are also harder to misuse. In April 2006, the FDA approved a transdermal patch for the treatment of ADHD called [[Daytrana]].<ref>Peck, P. (2006, [[7 April]]). FDA Approves Daytrana Transdermal Patch for ADHD. MedPage today. Retrieved [[April 7]], [[2006]], from http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/3027.</ref> ==Indications== [[Image:methylin2.jpg|thumb|left|Methylphenidate 10 mg Tablet (Mallinckrodt)]] Methylphenidate is a [[central nervous system]] (CNS) stimulant,<ref>{{cite journal | author = Fone KC | coauthors = Nutt DJ. | year = 2005 | month = Feb | title = Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder. | journal = Current opinion in pharmacology. | volume = 5 | issue = 1 | pages = 87-93 | pmid = 15661631 | doi = 10.1016/j.coph.2004.10.001}}</ref><ref>{{cite journal | author = Sharma RP | coauthors = Javaid JI, Pandey GN, Easton M, Davis JM. | year = 1990 | month = Apr | title = Pharmacological effects of methylphenidate on plasma homovanillic acid and growth hormone. | journal = Psychiatry research. | volume = 32 | issue = 1 | pages = 9-17 | pmid = 2190251 | doi = 10.1016/0165-1781(90)90130-W}}</ref><ref>{{cite journal | author = Shults T | coauthors = Kownacki AA, Woods WE, Valentine R, Dougherty J, Tobin T. | year = 1981 | month = May | title = Pharmacokinetics and behavioral effects of methylphenidate in Thoroughbred horses. | journal = American journal of veterinary research. | volume = 42 | issue = 5 | pages = 722-6 | pmid = 7258793 }}</ref> reducing impulsive behavior, and facilitating concentration on work and other tasks. Adults who have ADHD often report that methylphenidate increases their ability to focus on tasks and organize their lives. Methylphenidate has been found to have a lower incidence of side effects than [[dextroamphetamine]], a less commonly prescribed medication.<ref>Barbaresi, W.J., ''et al.'' (2006). "[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16511362&query_hl=1&itool=pubmed_docsum Long-Term Stimulant Medication Treatment of Attention-Deficit/Hyperactivity Disorder: Results from a Population-Based Study]". ''J Dev Behav Pediatr''. 2006 Feb;27(1):1-10.</ref> When prescribed at the correct dosage, methylphenidate is usually well tolerated by patients.<ref name="steele"/> A 2006 review assessing the safety of methylphenidate on the developing brain found that in animals with psychomotor impairments, structural and functional parameters of the dopamine system were improved with treatment.<ref>Grund T., et al. "[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16403217&query_hl=31&itool=pubmed_DocSum Influence of methylphenidate on brain development - an update of recent animal experiments]", ''Behav Brain Funct.'' 2006 [[January 10]];2:2.</ref> This indicates that in subjects with ADHD, methylphenidate treatment may positively support brain development. ==Pharmacology== Methylphenidate has binding affinity for both the [[dopamine transporter]] and [[norepinephrine transporter]], with the D-isomer displaying a prominent affinity for the latter. Both the dextro- and levorotary isomers displayed receptor affinity for the [[serotonergic]] 5HT<sub>1A</sub> and 5HT<sub>2B</sub> subtypes, though direct binding to the [[serotonin transporter]] was not observed.<ref>Markowitz JS "et al." (2006). "[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17201613&query_hl=2&itool=pubmed_docsum A Comprehensive In Vitro Screening of d-, l-, and dl-threo-Methylphenidate: An Exploratory Study]". "J Child Adolesc Psychopharmacol". 2006 Dec;16(6):687-98.</ref> The isomeric 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.{{Fact|date=May 2008}} ===Mode of action=== The means by which methylphenidate affects people diagnosed with ADHD are not well understood. Some researchers have theorized that ADHD is caused by a [[dopamine]] imbalance in the [[brain]]s of those affected. Methylphenidate is a norepinephrine and [[dopamine reuptake inhibitor]], which means that it increases the level of the dopamine [[neurotransmitter]] in the brain by partially blocking the dopamine transporter (DAT) that removes dopamine from the [[synapse]]s.<ref>Volkow N., ''et al.'' (1998). "[http://ajp.psychiatryonline.org/cgi/content/full/155/10/1325 Dopamine Transporter Occupancies in the Human Brain Induced by Therapeutic Doses of Oral Methylphenidate]". ''Am J Psychiatry'' 155:1325-1331, October 1998.</ref> This inhibition of DAT blocks the reuptake of dopamine and norepinephrine into the presynaptic neuron, increasing the amount of dopamine in the synapse. It also stimulates the release of dopamine and norepinephrine into the synapse. Finally, it increases the magnitude of dopamine release after a stimulus, increasing the salience of stimulus. The stimulants do not work paradoxically. They stimulate portions of the brain that are underactive by increasing dopamine and norepinephrine in the striatum and prefontal cortex. An alternate explanation which has been explored is that the methylphenidate affects the action of [[serotonin]] in the brain.<ref>{{cite journal |last=Gainetdinov |first=Raul R. |coauthors=Caron, Marc G. |year=2001 |month=March |title=Genetics of Childhood Disorders: XXIV. ADHD, Part 8: Hyperdopaminergic Mice as an Animal Model of ADHD |journal=Journal of the American Academy of Child & Adolescent Psychiatry |volume=40 |issue=3 |pages=380-382 |id= |url=http://www.med.yale.edu/chldstdy/plomdevelop/genetics/01margen.htm |accessdate=2006-11-11 }}</ref> === Side effects === Reported methylphenidate abuse [[Adverse drug reaction|side effects]] include [[psychosis]] (abnormal thinking or hallucinations), difficulty sleeping, mood swings, mood changes, nervousness, stomach aches, diarrhea, headaches, increased sex drive, lack of hunger (leading to weight loss) and dry mouth.<ref>[http://www.selfgrowth.com/articles/Virtue4.html Concerta: Benefits and Side Effects<!-- Bot generated title -->]</ref> Less common side effects include [[palpitations]], high blood pressure and pulse changes.{{Fact|date=May 2008}}<!-- Same cite as above or different? --> ==== Known or suspected risks to health ==== Researchers have also looked into the role of methylphenidate in affecting stature, with some studies finding slight decreases in height acceleration.<ref>Rao J.K., Julius J.R., Breen T.J., Blethen S.L. (1996). "[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9685452&query_hl=7 Response to growth hormone in attention deficit hyperactivity disorder: effects of methylphenidate and pemoline therapy]". ''Pediatrics''. 1998 Aug;102 (2 Pt 3):497-500.</ref> Other studies indicate height may normalize by adolescence.<ref>Spencer, T.J., ''et al.'' (1996)."[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8936912&query_hl=7 Growth deficits in ADHD children revisited: evidence for disorder-associated growth delays?]". ''J Am Acad Child Adolesc Psychiatry''. 1996 Nov;35(11):1460-9.</ref><ref>Klein R.G. & Mannuzza S. (1988). "[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3058089&query_hl=7 Hyperactive boys almost grown up. III. Methylphenidate effects on ultimate height]". ''Arch Gen Psychiatry''. 1988 Dec;45(12):1131-4.</ref> In a 2005 study, only "minimal effects on growth in height and weight were observed" after 2 years of treatment. "No clinically significant effects on vital signs or laboratory test parameters were observed."<ref>Wilens, T., ''et al.'' (2005). [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16175106&query_hl=11 ADHD treatment with once-daily OROS methylphenidate: final results from a long-term open-label study]". ''J Am Acad Child Adolesc Psychiatry''. 2005 Oct;44(10):1015-23.</ref> 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 chromosomal aberrations. They concluded that none of the compounds present a carcinogenic risk to humans.<ref>Teo, S.K., ''et al.'' (2003). "[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12742508&query_hl=17&itool=pubmed_docsum D-Methylphenidate is non-genotoxic in vitro and in vivo assays]". ''Mutat Res''. 2003 [[May 9]];537(1):67-79.</ref> 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 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 researchers indicated that their study was relatively small and their results needed to be reproduced in a bigger population for a definitive conclusion about the genotoxicity of methylphenidate to be drawn.<ref>El-Zein R.A., et al. (2005). "Cytogenetic effects in children treated with methylphenidate". Cancer Lett. 2005 [[December 18]];230(2):284-91.</ref> In response to the El-Zein study published in 2005, a team of six scientists from the Department of Child and Adolescent Psychiatry and Psychotherapy and the Department of Toxicology, [[University of Würzburg]], Würzburg, Germany began a more in-depth study. They sought to respond to the challenge noted above to attempt to replicate the results of El-Zein et al. in a larger study. Their paper was completed in 2006 and published in 2007 in [[Environmental Health Perspectives]] (EHP), the peer-reviewed journal of the United States' [[National Institute of Environmental Health Sciences]]. This study used a larger cohort and a longer period of follow-up and included a small group of long-term users, but otherwise used what researchers believed to be an identical methodology to that used by El-Zein et al. (They note that El-Zein et al. published a short study report and did not publish detailed descriptions of methodology.) After follow-ups at six months, the researchers found no evidence that methylphenidate might cause cancer, stating "the concern regarding a potential increase in the risk of developing cancer later in life after long-term MPH treatment is not supported".<ref>{{cite journal| title=Does Methylphenidate Cause a Cytogenetic Effect in Children with Attention Deficit Hyperactivity Disorder?| journal=Environmental Health Perspectives| authors=Walitza, Susanne, et al| date=June 2007 | volume=115| issue=6|pages=936–940| url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1892117| author=Walitza, Susanne| doi=10.1289/ehp.9866 <!--Retrieved from URL by DOI bot-->}}</ref> The effects of long-term methylphenidate treatment on the developing brains of children with ADHD is the subject of study and debate.<ref>{{cite journal| url=http://findarticles.com/p/articles/mi_m0NKT/is_1_25/ai_99698688/pg_4| title=ADHD & Women's Health - Attention-deficit hyperactivity disorder National Women's Health Report |quote= Although methylphenidate is perhaps one of the best-studied drugs available, with thousands of studies attesting to its longterm safety over the past 50 years, that hasn't stopped critics from raising alarms about the drug's long-term use on children's developing brains, particularly given research that finds the numbers of children taking the drug skyrocketing in recent years.|year=2003|month=February|accessdate=2007-11-03}}</ref><ref>{{cite journal| title= Nonpharmacological Interventions for Preschoolers With ADHD: The Case for Specialized Parent Training| url=http://depts.washington.edu/isei/iyc/sonuga_19.2.pdf| format= PDF| authors= Edmund J. S. Sonuga-Barke, Margaret Thompson, Howard Abikoff, Rachel Klein, Laurie Miller Brotman| journal= Infants & Young Children| volume =19| issue= 2| pages= 142–153| quote= While most recent studies suggest that methylphenidate is relatively well-tolerated by young children, some suggest that side effects might be more marked in preschoolers than in school-aged children (Firestone, Musten, Pisterman, Mercer, & Bennett, 1998). Furthermore, some researchers have argued that there is the potential for negative long-term effects on the developing brains of young children chronically medicated (Moll, Rothenberger, Ruther, & Huther, 2002).}}</ref> Although the safety profile of short-term methylphenidate therapy in clinical trials has been well established, repeated use of psychostimulants such as methylphenidate is less clear. In the United States, methylphenidate is classified as a [[Controlled Substances Act|Schedule II]] [[controlled substance]], the designation used for substances that have a recognized medical value but present a high likelihood for abuse because of their addictive potential. Internationally, methylphenidate is a Schedule II drug under the [[Convention on Psychotropic Substances]].<ref>{{PDFlink|[http://www.incb.org/pdf/e/list/green.pdf Green List: Annex to the annual statistical report on psychotropic substances (form P)]|1.63&nbsp;MB}} 23rd edition. August 2003. International Narcotics Board, Vienna International Centre. Accessed [[2 March]] [[2006]]</ref> Methylphenidate has been used illegally by students for whom the drug has not been prescribed, to assist with coursework and examinations.<ref>Pittsburgh Tribune-Review. "[http://pittsburghlive.com/x/tribune-review/trib/regional/s_265518.html More students abusing hyperactivity drugs]".</ref> The use of ADHD medication in children under the age of 6 has not been studied. Severe hallucinations may occur. ADHD symptoms include hyperactivity and difficulty holding still and following directions; these are also characteristics of a typical child under the age of 6. For this reason it may be more difficult to diagnose young children, and caution should be used with this age group.<ref>[http://members.kaiserpermanente.org/kpweb/healthency.do?hwid=hw166083 Attention Deficit Hyperactivity Disorder (ADHD)]</ref> On [[March 22]], [[2006]] the FDA Pediatric Advisory Committee decided that medications using methylphenidate ingredients do not need black box warnings about their risks, noting that "for normal children, these drugs do not appear to pose an obvious cardiovascular risk."<ref>[http://www.fda.gov/ohrms/dockets/ac/06/minutes/2006-4210m_Minutes%20PAC%20March%2022%202006.pdf Minutes of the FDA Pediatric Advisory Committee]. [[March 22]], [2006].</ref> Previously, 19 possible cases had been reported of [[Cardiac arrest]] linked to children taking methylphenidate<ref>[http://www.newscientist.com/channel/health/mg18925393.300.html ''New Scientist'' [[18 February]] [[2006]]]</ref> and the Drug Safety and Risk Management Advisory Committee to the [[FDA]] recommend a [[Black box warning|"black-box" warning]] in 2006 for stimulant drugs used to treat attention deficit/hyperactivity disorder.<ref>Minutes of the FDA Pediatric Advisory Committee, [[March 22]], [2006]</ref> According to a small study conducted by the Society of Nuclear Medicine, the use of methylphenidate in certain individuals for reasons outside of its intended clinical applications may adversely affect cognitive performance. Specifically, methylphenidate positively affected brain glucose metabolism in subjects who performed well at baseline on an accuracy-controlled cognitive task, but caused further deterioration of mental processing in subjects who performed poorly at baseline. In other words, certain individuals without ADHD who take the drug to enhance concentration and focus may inadvertantly make things worse.<ref>[http://www.sciencedaily.com/releases/2008/06/080616115843.htm]</ref> However, in a paper published in Biological Psychiatry ([[June 24]], [[2008]] online), researchers report that methylphenidate fine-tunes the functioning of neurons in the [[prefrontal cortex]] - a brain region involved in attention, decision-making and impulse control - while having few effects outside it. The team studied PFC neurons in rats under a variety of methylphenidate doses, including one that improved the animals' performance in a working memory task of the type that ADHD patients have trouble completing. Using microelectrodes, the scientists observed both the random, spontaneous firings of PFC neurons and their response to stimulation of the [[hippocampus]]. When they listened to individual PFC neurons, the scientists found that while cognition-enhancing doses of methylphenidate had little effect on spontaneous activity, the neurons' sensitivity to signals coming from the hippocampus increased dramatically. Under higher, stimulatory doses, on the other hand, PFC neurons stopped responding to incoming information.<ref>[http://newswise.com/articles/view/542042/ Study Uncovers How Ritalin Works in Brain to Boost Cognition, Focus Attention] Newswise, Retrieved on June 24, 2008.</ref> ==Delivery formulations== [[Image:Ritalin Pill.jpg|thumb|right|Ritalin 10mg Pill (Ciba/Novartis)]] All media are in milligrams. ===Tablet=== *'''Ritalin:''' 5, 10 or 20mg tablets. *'''Ritalin SR:''' 20mg controlled-release tablets. *'''Attenta:''' 10mg tablets. *'''Methylin:''' 5, 10 or 20mg tablets. *'''Methylin ER:''' 10 and 20mg controlled-release tablets. *'''Metadate ER:''' 10 and 20mg controlled-release tablets. *'''Concerta:''' 18, 27, 36 and 54mg controlled-release tablets. <ref>[http://www.concerta.net/concerta/assets/prescribing_info.pdf Full Prescribing Information for Concerta]. (215 [[Kibibyte|KiB]])</ref> (goes off patent in 2018)<ref>[http://adhd.emedtv.com/concerta/generic-concerta.html Generic Concerta<!-- Bot generated title -->]</ref> *'''Equasym:''' 5, 10, 20 or 30mg tablets. *'''Rubifen:''' 5, 10 or 20mg tablets. ===Capsules=== *'''Ritalin LA:''' 10, 20, 30 or 40mg controlled-release capsules. *'''Metadate CD:''' 10, 20, 30, 40 or 60mg controlled-release capsules. ===Patches=== *'''[[Daytrana]]''' 10, 15, 20 or 30mg controlled-release patches. ==Criticism== {{main|Attention-deficit hyperactivity disorder controversies}} [[Image:Ritalin Bottle.jpg|thumb|right|A Japanese Bottle Of Ritalin]] Methylphenidate is frequently used in the treatment for [[ADHD]], and as such criticism of the drug is typically related to the controversy about ADHD. Generally criticism of methylphenidate revolves around the alleged or established side effects. There are also concerns about illicit use of the drug and the ethics of giving [[psychotropic]] drugs to children to reduce ADHD symptoms.<ref>Lakhan SE; Hagger-Johnson G. [http://www.cpementalhealth.com/content/3/1/21 The impact of prescribed psychotropics on youth]. ''Clinical Practice and Epidemiology in Mental Health'' 2007;3(21).</ref> Others wonder if the medication is a gateway drug to substance abuse although this contention has been discredited.<ref name="Wilens">Wilens, T.E.., ''et al.'' (2003). "[http://pediatrics.aappublications.org/cgi/gca?sendit=Get+All+Checked+Abstract(s)&SEARCHID=1041880066942_4290&FULLTEXT=stimulant&VOLUME=111&ISSUE=1&JOURNALCODE=&FIRSTINDEX=0&hits=10&RESULTFORMAT=&gca=111/1/179&gca=111/1/97#111/1/179 Does Stimulant Therapy of Attention-Deficit/Hyperactivity Disorder Beget Later Substance Abuse? A Meta-analytic Review of the Literature]". ''PEDIATRICS. 2003 Vol. 111 No. 1'':pp. 179-185 </ref><ref name="Barkley">Russell A. Barkley, PhD,''et al.'' (2003). "[http://pediatrics.aappublications.org/cgi/gca?sendit=Get+All+Checked+Abstract(s)&SEARCHID=1041880066942_4290&FULLTEXT=stimulant&VOLUME=111&ISSUE=1&JOURNALCODE=&FIRSTINDEX=0&hits=10&RESULTFORMAT=&gca=111/1/179&gca=111/1/97#111/1/97 Does the Treatment of Attention-Deficit/Hyperactivity Disorder With Stimulants Contribute to Drug Use/Abuse? A 13-Year Prospective Study]". ''PEDIATRICS. 2003 Vol. 111 No. 1'': pp. 97-109 </ref> According to an article in the ''[[Los Angeles Times]]'', "the uproar over Ritalin was triggered almost single-handedly by the [[Scientology]] movement."<ref name="LA Times">{{cite news | first=Joel | last=Sappell | coauthors= Welkos, Robert W. | url=http://www.latimes.com/news/local/la-scientology062990a,1,6085874,full.story?coll=la-news-comment | title=Suits, Protests Fuel a Campaign Against Psychiatry | work=[[Los Angeles Times]] | page=A48:1 | date=[[1990-06-29]] | accessdate=2006-11-29}} Backup copy [http://www.cs.cmu.edu/~dst/Library/Shelf/la90/la90-6b.html link here]</ref> The [[Citizens Commission on Human Rights]], an antipsychiatry group associated with Scientology, conducted a major campaign against Ritalin in the 1980s and lobbied Congress for an investigation of Ritalin.<ref name="LA Times" /> ==See also== *[[Ethylphenidate]] *[[Psychoactive drug]] *[[Stimulant]] *[[Amphetamine]] *[[Methamphetamine]] *[[Benzedrine]] *[[Controversy about ADHD]] *[[Pemoline]] ==References== {{Reflist|2}} ==External links== * [http://www.bnl.gov/bnlweb/pubaf/pr/1998/bnlpr092998.html Department of Energy 1998 [[September 29]] press release on Ritalin] at [[Brookhaven National Laboratory]] * [http://www.Erowid.org www.Erowid.org] Online library of [[psychoactive]] plants, chemicals and related topics from [[Erowid.org]] * [http://www.HarmReduction.org www.HarmReduction.org] A coalition of [[harm reduction]] advocates with resources and insightful help for those dealing with drug issues as well as those trying to provide help.] * [http://www.DanceSafe.org www.DanceSafe.org] A community-driven information project from the rave culture. * [http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Ritalin_Helps_Doctor_Beat_His_Cancer-Related_Fatigue.asp Ritalin Helps Doctor Beat His Cancer-Related Fatigue], 2002/06/13, from Cancer.org "Writing in the medical journal The Oncologist (Vol.7: 96), Robert Wharton MD, a pediatrician, described his battle with cancer and the overwhelming fatigue he experienced." * [http://www.myaddiction.com/ritalin_addiction.html Ritalin addiction resource] from [[Myaddiction.com]] {{Phenethylamines}} {{Stimulants}} {{Psychostimulants, agents used for ADHD and nootropics}} [[Category:Class A drugs]] [[Category:Class B drugs]] [[Category:Phenethylamines]] [[Category:Stimulants]] [[Category:Sympathomimetic amines]] [[Category:Piperidines]] [[Category:Dopamine reuptake inhibitors]] [[Category:Drug culture]] [[Category:Psychiatry]] [[Category:Drug addiction]] {{Link FA|es}} [[cs:Ritalin]] [[de:Methylphenidat]] [[es:Metilfenidato]] [[fa:ریتالین]] [[fr:Méthylphénidate]] [[it:Metilfenidato]] [[he:מתילפנידאט]] [[nl:Methylfenidaat]] [[ja:メチルフェニデート]] [[no:Metylfenidat]] [[pl:Metylfenidat]] [[pt:Metilfenidato]] [[ru:Метилфенидат]] [[sk:Metylfenidát]] [[fi:Metyylifenidaatti]] [[sv:Metylfenidat]] [[zh:哌甲脂]]