Dexmethylphenidate is an isomer of methylphenidate , a medicine used to treat children with ADHD. This variant of the well-known stimulant drug seems to work better than the original, and its use seems to be spreading.

In this article we explain what dexmethylphenidate is and what effects it has, what its mechanism of action is, what adverse effects and interactions are to be taken into account, and what role it plays in addiction and dependence.

What is dexmethylphenidate and what effects does it have?

Dexmethylphenidate or d-threemethylphenidate is an isomeric variant of methylphenidate, a drug commonly used in people with attention deficit hyperactivity disorder (ADHD).

There are two isomers of methylphenidate: d-threo-methylphenidate and l-threo-methylphenidate, two compounds that differ from the original molecule by small adjustments in the molecular chemical structure, resulting in some drug properties being different. It appears that only d-threemethylphenidate would be the clinically active ingredient.

In Spain, the variant of methylphenidate that is marketed is a mixture of the two isomers, the racemic mixture (d,l)-threo-methylphenidate. However, in other countries, the dexmethylphenidate variant is already being used, which would exclusively provide the therapeutic psychostimulant effects , avoiding the undesirable cardiovascular and anorexic (appetite suppressant) effects and reducing the potential for abuse of the substance.

This variant of methylphenidate is marketed under the name Focalin and, like its analogue, is used to treat individuals suffering from ADHD (from age 5). Normally, if no benefit is observed after 4 weeks of consumption, it is usually discontinued.

The effects of dexmethylphenidate last from 4 to 6 hours (except for the long-acting formulation, which lasts up to 12 hours).

Mechanism of action

Although the mechanism of action of dexmethylphenidate would not be fully clarified, it is suggested that it would exert its effect by amplifying the dopaminergic signal by blocking its reuptake at the presynaptic level.

This drug would also be able to block the reuptake of another neurotransmitter, noradrenaline , by binding to its specific carrier. The overall effect is an increase in the subject’s attentional and alert level. This can be measured with devices that pick up low voltage waves.

On the other hand, dexmethylphenidate increases the excitatory mechanisms of the brain, improving concentration, motor coordination and impulse control in the subject. In patients with ADHD, the effects of dexmethylphenidate are attributed to the ability of this drug to improve the inhibitory mechanisms of the frontosubcortical circuits in which dopamine is involved.

The compound would exert a regulatory action on the frontal cortex and subcortical structures , such as the ventral part of the striated nucleus, in the basal ganglia. In this brain area is also the nucleus accumbens, a structure in which dopamine would act limiting the processing of the information to be processed, with the consequent improvement in the focus of the subject’s attention.

Side effects

Generally, although a drug like dexmethylphenidate is fairly well tolerated, side effects can be seen at the start of treatment (as with classic methylphenidate), although they are usually transient. Sometimes, delaying or reducing the dose taken may be enough to reduce adverse reactions.

The patient may suffer from abdominal pain, changes in blood pressure and heart rate, and even nervous tics (the risk, in this sense, is minimal). However, studies indicate that the side effects are mild and limited.

Some studies had postulated a possible relationship between methylphenidate intake and a suppression in growth hormone and prolactin secretion. However, this relationship has now been dismissed, as child patients treated with the drug would return to normal size in adolescence.

However, the consumption of dexmethylphenidate can cause a number of side effects that should be noted:

  • Nervousness and anxiety
  • Irritability
  • Headache
  • Upset stomach
  • Sleeping difficulties
  • Dizziness
  • Nausea and Vomiting
  • Loss of appetite
  • Weight loss

Drug Interactions

People being treated with dexmethylphenidate should be aware of possible drug interactions. It is very important to always follow the guidelines indicated by the health professional of reference.

Below, we will see some of the drugs that are contraindicated if you are being treated with dexmethylphenidate :

  • Isocarboxazid
  • Iobenguano
  • Linezolid
  • Phenelzine
  • Procarbazine
  • Rasagiline
  • Safinamide
  • Selegiline (and transdermal selegiline)
  • Tranylcypromine

Addiction and dependence

Methylphenidate is a stimulant drug with a certain power of addiction and dependence, similar to that which amphetamine may have . For this reason, the consumption of this type of substance can generate dependence, both physical and psychological, which is more likely when dexmethylphenidate is used in high doses or as a recreational drug.

When used above the medical dose range, stimulants can trigger psychosis processes , especially in predisposed people. With the consumption of almost all drugs with addictive potential, a protein called FosB is activated which is part of the brain’s reward circuit (in the nucleus accumbens).

This protein combines with others and binds to receptors that promote the expression of certain neuronal genes which, in turn, modify the expression and activity of other neuronal groups, generating changes of an epigenetic nature (gene expression would be altered by the addition of certain molecules to the DNA).

In several studies, dexmethylphenidate has been shown to be beneficial as replacement therapy for people with methamphetamine addiction and dependence . In addition, methylphenidate and amphetamines have also been investigated as chemical replacements for treating people with cocaine addiction, in the same way that methadone is used as a replacement drug for physical heroin dependence.

Bibliographic references:

  • Adler, L. A., Spencer, T., McGough, J. J., Jiang, H., & Muniz, R. (2009). Long-term effectiveness and safety of dexmethylphenidate extended-release capsules in adult ADHD. Journal of Attention Disorders, 12(5), 449-459.
  • Brams, M., Muniz, R., Childress, A., Giblin, J., Mao, A., Turnbow, J., … & Silva, R. (2008). A randomized, double-blind, crossover study of once-daily dexmethylphenidate in children with attention-deficit hyperactivity disorder. CNS drugs, 22(8), 693-704.