How can a stimulant be used to treat hyperactivity?

(Adapted from wikipedia)

Methylphenidate (Ritalin) works by blocking the reuptake of dopamine into nerve terminals (as well as stimulating the release of dopamine from dopamine nerve terminals) resulting in increased dopamine levels in the synapse.


Neurons showing synapses and receptors . image: wikipedia

The onset of central nervous system effects occurs rapidly after intake of methylphenidate and persist for about 4 hours.

The mechanism of action and chemical structure of methylphenidate is extremely similar to cocaine with usual doses of both drugs occupying 50% of dopamine transporters. 

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 (stress hormone) 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.

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.


Chemical structure of Ritalin. image: wikipedia

An alternate explanation which has been explored is that the methylphenidate affects the action of serotonin in the brain.

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.

It is commonly asked why a stimulant should be used to treat hyperactivity, which seems paradoxical.

MRIs of ADHD brains previously drugged with stimulants show decreased activity in the brain centers critical to concentration and impulse control.

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.

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