Pramipexole, sold under the brand Mirapex among others, is medication used to treat Parkinsons disease (PD) and restless legs syndrome (RLS). In Parkinsons disease it may be used alone or together with levodopa. It is taken by mouth. Pramipexole is a dopamine agonist of the non-ergoline class.Studies have shown detrimental side effects resulting from off-label use of pramipexole or other dopamine agonists in treating clinical depression.Pramipexole was approved for medical use in the United States in 1997. Use in pregnancy and breastfeeding is of unclear safety. It is available as a generic medication. In 2019, it was the 166th most commonly prescribed medication in the United States, with more than 3 million prescriptions. Medical uses
Pramipexole is used in the treatment of Parkinsons disease (PD) and restless legs syndrome (RLS). Use in pregnancy and breastfeeding is of unclear safety.It is occasionally prescribed off-label for depression. Its effectiveness as an antidepressant may be a product of its strong partial agonistic activity on and preferential occupation of dopamine D3 receptors at low doses (see table below); as well, the drug has been shown to desensitize the inhibitory D22 autoreceptors but not the postsynaptic D2 receptors, leading to an increase in dopamine and serotonin levels in the prefrontal cortex.
Chronic administration of pramipexole may also result in desensitization of D3 autoreceptors, leading to reduced dopamine transporter function, "We show that prolonged administration of pramipexole (0.1mg/kg/day, 6 to 21 days) [equivalent to a low ~0.5 mg/day human dose], a preferential D3R agonist, leads to a decrease in DA [dopamine] uptake in mouse striatum that reflects a reduction in DAT [dopamine transporter] affinity for DA in the absence of any change in DAT density or subcellular distribution ... These observations provide novel insights into the long-term antiparkinson, antidepressant and additional clinical actions of pramipexole and other D3R agonists".As summarized in the following commentary, trials have shown mixed results, "Dopamine agonists, such as pramipexole—a relatively selective dopamine D3 receptor agonist—are thus potential treatments for depression, especially anhedonic depression. D3 receptors are found in the mesolimbic system, which in turn has been implicated in the motoric and hedonic deficits in depression ... The first randomized controlled trial in patients with non-treatment-resistant major depressive disorder, by Corrigan et al., evaluated three dosages of pramipexole. The lowest dosage (0.375 mg/day) did not differentiate from placebo. The efficacy of the highest dosage (5.0 mg/day) was not evaluable, because of a 58% attrition rate. The third dosage (1.0 mg/day) was more effective than placebo ... Cusin et al. compared adjunctive adjunctive pramipexole with placebo in an 8-week randomized double-blind trial with 60 outpatients with major depression for whom at least one adequate antidepressant medication trial (mean, two trials) had failed.