Methylphenidate hydrochloride
[CAS# 298-59-9]

Identification

• Classification: API >> Nervous system medication >> Other nervous system medication
• Name: Methylphenidate hydrochloride
• Synonyms: Methyl phenyl(piperidin-2-yl)acetate hydrochloride
• Molecular Formula: C₁₄H₁₉NO₂^.HCl
• Molecular Weight: 269.77
• CAS Registry Number: 298-59-9
• EC Number: 206-065-3
• SMILES: COC(=O)C(C1CCCCN1)C2=CC=CC=C2.Cl

Properties

• Melting point: 224 - 226 ºC (Expl.)
• Refraction index: water:10 mM (Expl.)

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Hazard Statements: H302-H317-H334-H336
• Precautionary Statements: P233-P260-P261-P264-P270-P271-P272-P280-P284-P301+P317-P302+P352-P304+P340-P319-P321-P330-P333+P317-P342+P316-P362+P364-P403-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Respiratory sensitization	Resp. Sens.	1	H334
Specific target organ toxicity - single exposure	STOT SE	3	H336
Skin sensitization	Skin Sens.	1B	H317
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Germ cell mutagenicity	Muta.	2	H341
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H312
Reproductive toxicity	Repr.	1A	H360
Acute toxicity	Acute Tox.	3	H331
Flammable solids	Flam. Sol.	2	H228
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	3	H301
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Skin sensitization	Skin Sens.	1	H317

• Controlled Substance: DEA Drug Code Number: 1724

Discovory and Applicatios

Methylphenidate hydrochloride is a central nervous system stimulant that has been widely studied for its therapeutic use in attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. The compound is the hydrochloride salt of methylphenidate, a piperidine derivative structurally related to amphetamines but with a distinct pharmacological profile. It was first synthesized in the 1940s during efforts to develop new psychostimulants for medical use. Early investigations showed that methylphenidate hydrochloride produced stimulation of the central nervous system without the pronounced sympathomimetic side effects seen with amphetamine, leading to further exploration of its therapeutic potential.

The discovery of methylphenidate hydrochloride is closely associated with the Swiss pharmaceutical company Ciba, which developed and introduced the drug under the trade name Ritalin in the mid-1950s. Initial clinical applications targeted conditions such as depression, chronic fatigue, and lethargy associated with medical illness. However, by the 1960s its use shifted toward pediatric psychiatry, particularly in the treatment of what was then described as hyperkinetic reaction of childhood, now recognized as ADHD. Clinical trials demonstrated that the compound improved attention span, reduced impulsivity, and enhanced behavioral control in affected children, establishing it as a cornerstone therapy.

Methylphenidate hydrochloride acts primarily by blocking the reuptake of dopamine and norepinephrine in the brain, particularly in the prefrontal cortex, thereby increasing the availability of these neurotransmitters in synaptic clefts. This pharmacological effect improves signal transmission in pathways related to attention, executive function, and behavioral regulation. Unlike amphetamines, which also promote neurotransmitter release, methylphenidate exerts a more selective reuptake inhibition, contributing to differences in efficacy and tolerability.

The clinical applications of methylphenidate hydrochloride have expanded beyond childhood ADHD. It has been shown to be effective in adults with ADHD, a condition that often persists beyond adolescence. In addition, the compound is used in the treatment of narcolepsy, where it alleviates excessive daytime sleepiness and improves wakefulness. Research has also investigated its potential role in conditions such as traumatic brain injury, depression resistant to conventional antidepressants, and cognitive deficits in certain neurological disorders, although these uses are less established.

Methylphenidate hydrochloride is available in various formulations, including immediate-release tablets, sustained-release tablets, and extended-release capsules, which allow for flexible dosing and duration of action tailored to individual patient needs. This development of controlled-release technologies was a major advance in improving adherence and minimizing side effects, as it reduced the frequency of dosing and provided more consistent therapeutic effects throughout the day.

Despite its clinical value, methylphenidate hydrochloride has been the subject of extensive discussion concerning safety, abuse potential, and long-term use. As a Schedule II controlled substance in many countries, it carries a risk of misuse and dependence, particularly when taken in high doses or by routes other than prescribed. Research has shown that therapeutic use under medical supervision is generally safe and effective, but concerns about diversion and nonmedical use have led to careful regulatory control.

The discovery and development of methylphenidate hydrochloride represent a landmark in psychopharmacology. Its introduction provided an effective and relatively well-tolerated option for ADHD, fundamentally shaping the modern management of the disorder. Decades of research and clinical use have solidified its role as a first-line treatment, while ongoing studies continue to refine understanding of its mechanisms, optimize delivery systems, and assess its long-term impact on patients.

References

2020. The rate of dasotraline brain entry is slow following intravenous administration. Psychopharmacology, 237(11).
DOI: 10.1007/s00213-020-05623-7

2013. The impact of methylphenidate on seizure frequency and severity in children with attention-deficit-hyperactivity disorder and difficult-to-treat epilepsies. Developmental Medicine and Child Neurology, 55(7).
DOI: 10.1111/dmcn.12121

2013. Methylphenidate and/or a nursing telephone intervention for fatigue in patients with advanced cancer: a randomized, placebo-controlled, phase II trial. Journal of Clinical Oncology, 31(19).
DOI: 10.1200/JCO.2012.45.3696