Drug info - Comprehensive Methylphenidate Information

[tdawe1]

MUCH CREDIT TO "GFORCE" AND HIS THREAD IN THE ADDERALL SECTION, I HAVE STOLEN HIS IDEAS AND APPLIED THEM TO METHYLPHENIDATE

Comprehensive Methylphenidate Information

Inspired by a thread on the Adderall subsection, again there is no thread that provides a summary/FAQ about how methylphenidate (Ritalin) work. Much credit must go to GForce for making the Adderall equivilant to this, as I will use his ideas for sections and information.

General Information

Methylphenidate (MPH), is the world's most commonly prescribed psychostimulant. It was first synthesized in 1948 and has been used in the treatment of ADHD since the 1960s. Due its widespread use and long lifespan, methylphenidate is a very well understood drug in terms of long term effects and side effects. It is used primarily in the treatment of ADHD and narcolepsy, although it has off label uses in depression, lethargy and obesity.

There are several different release formulations of methylphenidate, these are the most common:

* Ritalin - Instant release version of racemic methylphenidate. Available in 5, 10 or 20mg tablets.

* Ritalin SR - Extended release version of racemic methylphenidate. Available in 20mg tablets

* Concerta - Complex extended release version of racemic methylphenidate. Available in 18, 27, 36 and 54mg osmotic release tablets. Concerta is under patent until 2018.

* Focalin (XR) - Standard and extended release versions of dexmethylphenidate, the right handed isomer of MPH. It is typically given in 10-20mg doses to children and 20-40mg doses to adults.



All forms of methylphenidate are Schedule II controlled substances in the US, Class B in the UK, which means use and possession without a prescription is illegal, and is on a par with methamphetamine or cocaine.

Chemistry

Racemic methylphenidate is the active ingredient in most generic and brand name medications, save Focalin. It is a 50:50 mix of dexmethylphenidate (the right handed isomer) and levomethylphenidate (the left handed isomer). Focalin is pure dexmethylphenidate.

The methylphenidate molecule

Originally Posted by Wikipedia

Methylphenidate occurs in four different enantiomers, each showing its own structure. One pair of threo isomers and one pair of erythro are distinguished, from which only d-threo-methylphenidate exhibits the pharmacologically usually desired effects.
The 3D pictures on the right are of the threo enantiomers. When the drug was first introduced it was sold as a 3:1 mixture of erythro:threo diastereomers. The erythro diastereomers are also pressor amines.

Methylphenidate is a chain substituted amphetamine derivative, although more chemically similar to cocaine (having a very similar method of action). It has been shown to increase levels of dopamine (DA) and norepinephrine (NE) in the synapse. Methylphenidate binds to the dopamine (DAT) and norepinephrine (NET) transporters, inhibiting the reuptake. A usual dose of methylphenidate blocks around ~50% of dopamine transporters. Dexmethylphenidate has approximately the same efficacy as the racemic parent compound on DAT but shows less affinity on NET. Both the dextro- and levorotary enantiomers displayed receptor affinity for the serotonergic 5HT1A and 5HT2B subtypes, though direct binding to the serotonin transporter is not observed.

How can a stimulant help treat hyperactivity?

Originally Posted by wikipedia

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 brains 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 synapses.[106] 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. An alternate explanation which has been explored is that the methylphenidate affects the action of serotonin in the brain.[97][107] However, benefits with other stimulants which have a different mechanism of action indicates that support for a deficit in specific neurotransmitters is unsupported and unproven by the evidence and remains a speculative hypothesis.[108]
It is commonly asked why a stimulant should be used to treat hyperactivity, which seems paradoxical. However, MRIs of ADHD brains show decreased activity in the brain centers critical to concentration and goal-directed activities.
One study finds that methylphenidate reduces the increases in brain glucose metabolism during performance of a cognitive task by about 50%. This suggests that, similar to increasing dopamine and norepinephrine in the striatum and prefrontal cortex, methylphenidate may focus activation of certain regions and make the brain more efficient. This is consistent with the observation that stimulant drugs can enhance attention and performance in some individuals. If brain resources are not optimally distributed (for example, in individuals with ADHD or sleep deprivation), improved performance could be achieved by reducing task-induced regional activation. Stimulant delivery when brain resources are already optimally distributed may then adversely affect performance.

Effects

Methylphenidate is a potent CNS stimulant. As stated earlier, it is a strong reuptake inhibitor of dopamine and norepinephrine, resulting in increased levels of these chemicals available to the brain, causing an increase in concentration and motivation. There are side effects associated with the use of methylphenidate:

Originally Posted by wikipedia

The most common side effects of taking methylphenidate are nervousness and insomnia. Other reactions include:
* Abdominal pain
* Acne vulgaris
* Addiction and drug dependence
* Angina
* Appetite loss
* Blood pressure and pulse changes, both up and down
* Cardiac arrhythmia
* Diaphoresis (sweating)
* Dizziness
* Drowsiness
* Dyskinesia
* Stunted growth
* Headaches
* Hypersensitivity (including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic purpura)
* Nausea
* Palpitations
* Pupil dilation
* Tachycardia

In addition, suicidal thoughts, personality changes, and weight loss may be experienced during prolonged therapy. Very rare effects include reports of Tourette's syndrome, seizures, toxic psychosis, and neuroleptic malignant syndrome.

Drug Interactions

Methylphenidate has a number of reactions with other drugs:

* Antidepressants - taken in conjuction with methylphenidate, antidepressants can cause hypertension, convulsions and hypothermia

* Adrenergic agonists - intake of adrenergic agonist drugs or permoline in conjuction with methylphenidate increases the risk of liver toxicity

* Alcohol - When alcohol and methylphenidate are ingested together, the compound ethylphenidate is formed, very similar to cocaine and alcohol form cocaethylene. Coingestion of alcohol (ethanol) also increases the blood plasma levels of d-methylphenidate by up to 40%.[

* MAO inhibitors - Monoamine oxidase inhibitors slow the metabolisim of methylphenidate. This slowing potentiates, "increasing their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of neurological toxic effects and malignant hyperpyrexia can occur, sometimes with fatal results."

* Haloperidol - Haldol blocks the dopamine transporters, inhibiting the CNS stimulation effects of methylphenidate.

More information needed

General Usage

Methylphenidate is the world's most commonly prescribed stimulant, and also has wide recreational and utilitarian usage off label. Those that obtain it illegally often do not do so simply for it's cocaine like euphoric high, it is also often used off label for the increased mental focus, ability to stay awake for long periods without feeling tired, and motivation to do otherwise dull tasks. Methylphenidate has been shown to be habit forming (especially if used illicitly) so care should be taken in high dose medicinal use and regular recreational use.

Methylphenidate (and other prescription stimulants such as Adderall or Dexedrine) is commonly used as a study aid by students. Many students fake ADHD to gain a prescription or buy it illegally on the streets for it's ability to provide energy and motivation allowing them to study longer. Another use is to stay up and party longer despite consuming large quantities of alcohol at parties. Alcohol and methylphenidate consumed together forms ethylphenidate, having approximately the same efficacy as methylphenidate on the dopamine transporters but far less on norepinephrine NET. Both alcohol and methylphenidate cause dehydration, and methylphenidate can offset some side effects of alcohol, putting you at increased risk of alcohol poisoning if you do not keep track of how much you have drunk. Combining the two can be dangerous.

Methods of Administration

* Oral - Medicinal methylphenidate is meant to be ingested orally. Effects such as stimulation, motivation and increased concentration with be apparent for around 4-5 hours, with extended release formulations lasting up to 12 hours. This method is rarely used recreationally as it is uncommon for euphoria to be felt, however it is often used illegally by students using methylphenidate as a study aid or to stay awake longer.

* Insufflation - Most common method for recreational abuse, methylphenidate can be insufflated in powder form when crushed up for a faster onset and stronger rush effects, as well as a shorter duration. The effects typically hit within 10 minutes and strong euphoria and stimulation is present in correct dosages. Controlled release pills are often hard to crush, Concerta is nigh on impossible, however instant release and capsules with beads viable.

* Rectal 'plugging' - Uncommon method for recreational abuse, methylphenidate is crushed into powder form and dissolved into water, and a syringe is used (no needle) to administer. Not much is known about plugging MPH, but theoretically it should be between IV and IN (intranasal) use, indicating an intense rush and a short duration, hypothetically very similar to cocaine in this use.

* IV (intravenous) - Very uncommon but very potent method for recreational use. Due to the amount of binders and fillers in one pill, it is very unhealthy and dangerous to inject MPH. However, if conducted it is reportedly similar/stronger effects than IV cocaine. MPH is technically more potent than cocaine in its effects on the dopamine transporters, however cocaine's rush/euphoria is caused by its very fast action. IV administration makes up for this shortcoming of MPH making for an exceptionally intense euphoric rush. Short duration, assume ~1 hour.

Smoking Short, powerful and intense - SWIM's favoured method (he won't IV it), but a hassle to prepare. See this thread http://www.drugs-forum.com/forum/showthread.php?t=52232 for a very good guide.

Reputation Comments on this post:

	Good thread, with lots of information. It has already helped me.
	Excellent summary of information well deserving of rep.