Methylphenidate
Methylphenidate, sold under the brand names Ritalin (/ˈrɪtəlɪn/ RIT-ə-lin) and Concerta (/kənˈsɜːrtə/ kən-SUR-tə) among others, is a potent central nervous system (CNS) stimulant used medically to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, narcolepsy. It is a primary medication for ADHD (e.g. in the UK[15]); it may be taken by mouth or applied to the skin, and different formulations have varying durations of effect, commonly ranging from 2–4 hours.[2] For ADHD, the effectiveness of methylphenidate is comparable to atomoxetine[16][17][18][19] but modestly lower than amphetamines.[20][21][22][23]
"Ritalin" redirects here. Not to be confused with Ryetalyn.Clinical data
Ritalin, Concerta, others
MPH[1]
- AU: D
High[2]
High[3]
Central nervous system stimulant & norepinephrine–dopamine reuptake inhibitor
Insufflation: approx. 70% Oral: approx. 30% (range: 11–52%)
10–33%
2–3 hours[13]
- Instant-release: 3-4 hours
- Extended-release: 6-12 hours
Urine (90%)
C14H19NO2
233.311 g·mol−1
74 °C (165 °F) [14]
136 °C (277 °F) [14]
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.[9] Withdrawal symptoms may include chills, depression, drowsiness, dysphoria, exhaustion, headache, irritability, lethargy, nightmares, restlessness, suicidal thoughts, and weakness.[2]
Methylphenidate is believed to work by blocking the reuptake of dopamine and norepinephrine by neurons.[24][25] It is a central nervous system (CNS) stimulant of the phenethylamine and piperidine classes. It is available as a generic medication.[26] In 2021, it was the 43rd most commonly prescribed medication in the United States, with more than 15.2 million prescriptions.[27][28]
Etymology[edit]
The word methylphenidate is a portmanteau of the chemical name, Methyl-2-phenyl-2-(piperidin-2-yl) acetate.
The name "Ritalin" derives from Marguerite "Rita" Panizzon, the wife of Leandro Panizzon, who first synthesized the drug in 1944. Rita was the first person to take methylphenidate, and described its effects to her husband.[29]
Contraindications[edit]
Methylphenidate is contraindicated for individuals with agitation, tics, glaucoma, heart defects or a hypersensitivity to any ingredients contained in methylphenidate pharmaceuticals.[12]
Pregnant women are advised to only use the medication if the benefits outweigh the potential risks.[75] Not enough human studies have been conducted to conclusively demonstrate an effect of methylphenidate on fetal development.[76] In 2018, a review concluded that it has not been teratogenic in rats and rabbits, and that it "is not a major human teratogen".[77]
Interactions[edit]
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.[11] There are several case reports of methylphenidate inducing serotonin syndrome with concomitant administration of antidepressants.[100][101][102][103]
When methylphenidate is coingested with ethanol, a metabolite called ethylphenidate is formed via hepatic transesterification,[104][105] 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.[106][105]
Coingestion of alcohol also increases the blood plasma levels of d-methylphenidate by up to 40%.[107]
Liver toxicity from methylphenidate is extremely rare, but limited evidence suggests that intake of β-adrenergic agonists with methylphenidate may increase the risk of liver toxicity.[108]
History[edit]
Methylphenidate was first synthesized in 1944 and was approved for medical use in the United States in 1955.[145][146][147] It was synthesized by chemist Leandro Panizzon and sold by Swiss company CIBA (now Novartis).[145] He named the drug after his wife Margarita, nicknamed Rita, who used Ritalin to compensate for low blood pressure.[148] Methylphenidate was not reported to be a stimulant until 1954.[149][150] The drug was introduced for medical use in the United States in 1957.[151] Originally, it was marketed as a mixture of two racemates, 80% (±)-erythro and 20% (±)-threo, under the brand name Centedrin.[149] 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.[149][152][153][154] The erythro isomer was eliminated, and now modern formulations of methyphenidate contain only the threo isomer in a 50:50 mixture of d- and l-isomers.[149]
Methylphenidate was first used to allay barbiturate-induced coma, narcolepsy and depression.[155] It was later used to treat memory deficits in the elderly.[156] Beginning in the 1960s, it was used to treat children with ADHD based on earlier work, starting with the studies by American psychiatrist Charles Bradley[157] on the use of psychostimulant drugs, such as Benzedrine, with then called "maladjusted children".[158] 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.[159]
In 2000, Alza Corporation received US FDA approval to market Concerta, an extended-release form of methylphenidate.[11][160][161]
It was estimated that the number of doses of methylphenidate used globally in 2013 increased by 66% compared to 2012.[162] In 2021, it was the 43rd most commonly prescribed medication in the United States, with more than 15 million prescriptions.[27][163] It is available as a generic medication.[2]
Swiss "Ritalin" brand methylphenidate
Indian "AddWize" branded instant-release and extended-release formulations costing US$1.9 for a strip of instant-release and US$2.9 for a strip of AddWize extended-release
Clockwise from top: Concerta 18 mg, Medikinet 5 mg, Methylphenidat TAD 10 mg, Ritalin 10 mg, Medikinet XL 40 mg
