Methylphenidate is a stimulant drug generally prescribed to treat ADHD and narcolepsy, and has also been used to manage treatment-resistant depression, eating disorders, and as a maintenance drug for those addicted to cocaine or methamphetamine. It is available in both instant-release and a variety of extended-release formulations. Like amphetamine which has a similar molecular structure and comparable potency, the drug works by increasing the amounts of extracellular dopamine and norepinephrine. However, methylphenidate is notable in that it has a half life of just 2-3 hours, much shorter than that of either the dextro or levo isomers of amphetamine whose half lives exceed 10 hours.
[top]Introduction to Methylphenidate
Methylphenidate is a synthetic central nervous system stimulant--also well described as a substituted amphetamine, though its mechanism of action is distinct from the classical amphetamines-- which is prescribed worldwide for a variety of diagnoses, such as Attention-Deficit (Hyperactivity) Disorder, Postural Orthostatic Tachycardia Syndrome, Chronic Fatigue Syndrome, narcolepsy, depression, obesity and (rarely) Obsessive-Compulsive Disorder. It has been shown to possess neuroprotective effects. It is sold as a racemic mixture under the brand names Ritalin, Ritilana, Ritaline, Attenta, Penid, Ribufen, Concerta, Metadate, Methylin and Daytrana.
The compound itself is a member of the piperidine class, and despite not being a member of the same family, it bears some structural resemblance to amphetamine but its effects are likened to those of cocaine.
It is most commonly sold as the water-soluble salt, methylphenidate hydrochloride.
[top]DexmethylphenidateDexmethylphenidate is the dextrorotary enantiomer of methylphenidate. It it sold under the brand name Focalin. This differs from the typically racemic form, which is an equal mixture of dextrorotary and levorotary molecules.
[top]Use of Methylphenidate
Methylphendate can provide a very satisfying high, However, when repeatedly abused, the user can build a tolerance to this drug very quickly, a high tolerance will reduce both the recreational and medicinal value of the drug.
[top]Commonly prescribed forms of Methylphenidate
[top]Instant-ReleaseCommonly known as ‘Ritalin’ is the conventional and most commonly prescribed form ofmethylphenidate, It releases the full dose of methylphenidate into the users system almost immediately after consumption.
Ritalin 10mg (Novartis)
[top]Extended-ReleaseCommonly known as ‘Concerta’ releases a small portion of the methylphenidate immediately and gradually releases the rest over a 9 hour period. Concerta is considered more difficult to abuse, It needs to be altered for Instant-release before consumotion, it also somewhat limits the user to oral administration as it is unsuitable for Intranasal or Intravenous use.
[top]TransdermalDaytrana is a methylphenidate-containing patch which is designed to be placed on the hip so that the drug may be absorbed into the blood through the skin. The slow-release mechanism of transdermal patches intentionally decreases the recreational potential of a drug, but is ideal for treatment.
[top]Routes of Administration for MethylphenidateMethylphenidate can be taken in a number of ways, some being significantly less dangerous than others.
This is the most common (and arguably safest)- route of administration. Tablets are available in instant release and extended release forms; the latter is designed to give a continuous effect throughout the whole day without the need for re-dosing, however, the recreational value of unaltered Concerta is very minimal.
The oral bioavailability of methylphenidate ranges between 11-52%
[top]IntranasalyMethylphenidate can be insufflated through the nose, where it is absorbed into the bloodstream via mucous membranes. Snorting crushed tablets may cause damage to the inside of the nose via vasoconstriction by the drug itself and corrosion by binders used in pill manufacture. As with cocaine, it is reasonable to assume that long-term abuse in this manner may lead to permanent damage, including destruction of the septum, which separates the nostrils. Thus, it is advised that an extraction be performed to obtain a relatively pure methylphenidate hydrochloride before attempting this, though extraction may reduce, but does not eliminate the potential for damage.
[top]Intravenously injectedThis can be very hazardous and is highly unrecommended. It can very easily cause an overdose and can cause potentially permanent peripheral and arterial damage (especially in an un-purified form) as well as carrying other risks such as infections.
The effects and their intensity vary depending on tolerance, dosage, route of administration and how the individual responds to the drug but the effects most commonly consist of:
- Decreased hyperactivity
- Enhanced libido
- Lengthened attention span
- Mild empathy
- Mood lift
- Physical and mental stimulation
[top]Side-effectsSide-effects commonly include:
Methylphenidate has comedown effects similar to those of amphetamines and cocaine, though usually less severe, The comedown effects commonly include
- Abdominal pain
- Addiction (psychological)
- Chest pain
- Heart palpitations
- Loss of appetite
- Mydriasis (pupil dilation)
- Craving for more of the drug
- Dry mouth/Seemingly unquenchable thirst
- Excessive sweating
- Hoarse voice
- Jaw clenching/Teeth grinding
- Muscle pain
- Sore throat
|Therapeutic||5mg - 20mg|| || || |
|Moderate||15mg - 40mg|| || || |
|Strong||35mg - 60mg|| || || |
|Dangerous||>60mg|| || || |
Chronic abuse or very high doses can lead to auditory hallucinations and stimulant psychosis. The long-term effects of methylphenidate use are unknown.
[top]Methylphenidate Compared to AmphetamineAmphetamine is a drug with similar effects as methylphenidate; it has the same indications, especially ADD/ADHD. However, methylphenidate is not an amphetamine, despite structural resemblances. Amphetamine's action slightly differs from methylphenidate's insofar as it also promotes the release of neurotransmitters into the synapse and significantly affects serotonin.
A Drugs-Forum poll shows a significant majority of users preferring the effects of Adderall (mixed amphetamine salts) over methylphenidate.
Combining methylphenidate with alcohol (ethanol) can enhance euphoria, libido and sociability as well as counteracting alcohol's drowsiness. It also often makes the user feel less drunk than they really are, and can be dangerous for this reason.
Ethylphenidate is a homologue of methylphenidate, which has an ethyl - instead of a methyl - group attached to the single-bonded oxygen of the acetate. This is shown in the above diagram by an extra angle at the top-left, representing the replacement of the methyl's last hydrogen with one carbon and three hydrogens.
Ethylphenidate is created in the human body when ethanol and methylphenidate are ingested at the same time, by a process called transesterification. The liver removes the methyl from methylphenidate and the ethyl from ethanol. Methanol is an expected byproduct of this reaction, but in such insignificant quantities as to pose no real risk to the body, especially due to the presence of ethanol, which is an antidote to poisoning by the former. The same process results in the formation of cocaethylene when cocaine and alcohol are co-ingested.
Methylphenidate is a powerful stimulant in its own right but can be combined with others to enhance its efficacy or recreational value. This practice carries overdose dangers as dosage does not directly translate from methylphenidate to other substances, as well as potentially increased risks to the cardiovascular system and of psychosis.
Selective serotonin reuptake inhibitors are prescribed for the treatment of depression, anxiety and Obsessive-Compulsive Disorder. There are no serious dangers inherent to combining methylphenidate with an SSRI. Some antidepressants, such as venlafaxine (Effexor), also inhibit the reuptake of noradrenaline, which can cause feelings of agitation and panic attacks when combined with methylphenidate.
Monoamine oxidase inhibitors are last resort antidepressants which inhibit the action of an enzyme called monoamine oxidase (MAO). MAO's function involves deanimation through the oxidation of monoamine compounds (such as neurotransmitters serotonin, dopamine and noradrenaline), which renders them inactive. By inhibiting this enzyme, the levels of these monoamines increase.
Methylphenidate should never be taken with an MAOI, and up to two to six weeks or more after taking any MAOI, since the rise in dopamine, norepinephrine, and serotonin levels associated with methylphenidate usage could provoke hypertensive crisis, serotonin syndrome, stroke, heart attack and death. The clinical use of combinations of stimulants, such as methylphenidate, and MAOIs is exclusively done in a hospital setting under very close medical supervision.
[top]Pharmacology of Methylphenidate
LD50 : 190 mg/kg orally in mice (as the hydrochloride salt)
Methylphenidate is a dopamine and noradrenaline/norepinephrine reuptake inhibitor (DNRI). It competitively binds to the transporter proteins which remove these neurotransmitters from the synaptic cleft, thereby allowing them to agonise receptors for longer. This is similar to the mechanism by which SSRI antidepressants inhibit the reuptake of serotonin.
It's primary metabolic path is hepatic by the cytochrome P450 as a substrate inhibitor of enzyme CYP2D6.
Dopamine and Noradrenaline
Endogenous phenethylamine neurotransmitters.
[top]Chemistry of Methylphenidate
|Systematic (IUPAC) name:||α-Phenyl-2-piperidine-acetic acid methyl ester|
|Synonyms:||Mehtyl phenidylacetate, methyl α-phenyl-α-(2-piperidyl)acetate, methylphenidan; Ciba 4311b, Concerta, Equasym, Metadate, Ritalin (hydrochloride)|
|Molecular Formula:||C14H19NO2, C14H19NO2.HCl (hydrochloride)|
|Molar mass:|| 233.31 g/mol, 269.77 g/mol (hydrochloride) |
|CAS Registry Number:||113-45-1, 298-59-9 (hydrochloride)|
|Melting Point:||74-75 °C , 224-226°C (hydrochloride)|
|Boiling Point:||135-137°C @ 0.6 mmHg|
|Flash Point:||no data|
|Solubility:||Freebase soluble in alcohol, ethyl acetate, ether, acetone; Practically insoluble in water, petroleum ether. Hydrochloride freely soluble in water, methanol; Soluble in alcohol; Slightly soluble in acetone, chloroform.|
|Additionnal data:||pKa 8.9|
|Notes:||Hydrochloride aspect : white to off white powder|
[top]Reagent test results of Methylphenidate
|Reagent || color produced|
|Liebermann's || Orange|
Toxicity studies in rats indicate:
Overdose symptoms include:
|ROA || Value || Dose|
|ORL-RAT || LD50 || 367mg/kg-1|
|SCU-RAT || LD50 || 170mg/kg-1|
|IVN-RAT || LD50 || 50mg/kg-1|
|ORL-MUS || LD50 || 60mg/kg-1|
|IVN-MUS || LDLO || 40mg/kg-1|
|ORL-CHD || TDLO || 32mg/kg-1 6w-i|
- Chest pain
- Feeling faint/Unconsciousness
- Irregular or pounding heartbeat/Heart palpitations
- Paranoia/Panic attack
- Tremor/Ticks/Muscle Spasms
Investigated as a carcinogen, mutagen and teratogen. No evidence of such activity found. (expand + source)
- Stunted growth
Methylphenidate was first synthesised 1944 in Basel, Switzerland, by Ciba (Chemische Industrie Basel).
Popularity of Methylphenidate over time:
[top]Legal Status of Methylphenidate
[top]United NationsControlled as a schedule 2 drug as per the Misuse of Drug Regulations, 1988. Possession is only legal on prescription from a licensed medical practitioner, or on permission from the Minister of Health. Prescriptions cannot be repeated. Illegal possession can result in an unlimited fine and/or a prison sentence of up to seven years. (Misuse of Drugs Act 1984, section 8, subsection 1b)
[top]Central / South America
[top]The latest Methylphenidate threads
 Calculated from Atomic Weights of the Elements, 2007
 Merck Index, fifteenth edition (2013)
 Methylphenidate monograph
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