Pramipexole (INN, trade names Mirapex and Sifrol) is a medication indicated for treating Parkinson's disease and restless legs syndrome (RLS). It is also sometimes used off-label as a treatment for cluster headache or to counteract the problems with low libido experienced by some users of SSRI antidepressant drugs. Pramipexole has shown robust effects on pilot studies in a placebo-controlled proof of concept study in bipolar disorder. Pramipexole is classified as a non-ergoline dopamine agonist.

Mechanism of action

The basal ganglia is a region of the human brain involved in the regulation of body movement; hence, when components of the basal ganglia are damaged, disorders of body movement may occur.

Parkinson's disease is a neurodegenerative disease affecting the substantia nigra, a component of the basal ganglia. The substantia nigra has a high quantity of dopaminergic neurons, which are neurons that release the neurotransmitter known as dopamine. When dopamine is released, it may activate dopamine receptors in the striatum, which is another component of the basal ganglia. When neurons of the substantia nigra deteriorate in Parkinson's disease, the striatum no longer receives dopamine signals. As a result, the basal ganglia can no longer regulate body movement effectively and motor function becomes impaired.

By acting as an agonist to the dopamine receptors, pramipexole may directly stimulate dopamine receptors in the striatum, thereby restoring the dopamine signals needed for proper functioning of the basal ganglia. Any depressant effects are most likely the result of pramipexole binding to the D2 receptor subtype, which exhibits inhibitory behavior.

Pramipexole binds to dopamine receptors, with particularly high affinity for the D3 receptor subtype.

Adverse effects

Some of the more common side effects of pramipexole include:

  • Dizziness, lightheadedness, or fainting, especially when standing up (orthostatic hypotension)
  • Drowsiness
  • Hallucinations (seeing, hearing, or feeling things that are not there)
  • Weight gain
  • Weight loss
  • Nausea
  • Trouble in sleeping
  • Twitching, twisting, or other unusual body movements
  • Unusual tiredness or weakness

Several unusual adverse effects of this medication may include compulsive gambling, hypersexuality, and overeating. These side effects may be linked to the D3 receptor agonist activity of pramipexole. D3 receptors are located in brain regions involved in mood, behavior, and rewards.




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