Classics in Chemical Neuroscience: Pramipexole

Abstract

Pramipexole was first manufactured by Pharmacia and Upjohn in July 1997 under the United States brand names of Mirapex and Mirapex ER. Pramipexole is classified as a nonergoline aminobenzothiazole compound that selectively agonizes the dopamine D2-like receptor subfamily, which includes the D2, D3, and D4 receptor subtypes. Pramipexole is a unique compound in its therapeutic potential because it has D3-preferring properties. The D3 receptor target has implications in both motor and psychiatric symptoms of Parkinson’s disease, restless leg syndrome, and bipolar and unipolar depression. Currently, pramipexole is approved to treat signs and symptoms of idiopathic Parkinson’s disease and moderate to severe symptoms of primary restless leg syndrome. Parkinson’s disease is characterized by tremor, bradykinesia, rigidity, gait disorders, and a disturbance of posture due to a decrease in dopamine stores in the substantia nigra with the consequent presence of Lewy bodies. Restless leg syndrome is a neurologic sensorimotor disorder characterized by a compelling urge to move the body/limb to relieve this uncomfortable sensation. In this Review, we will discuss the synthesis, drug metabolism, pharmacology, adverse effects, history, and the importance of pramipexole to neuroscience and describe its role in therapy.

Pharmacological and Non-pharmacological Treatments of Sleep Disorders in Parkinson's Disease

“…They should be administered 2 to 3 hours before bedtime to relieve RLS in PD [ 73 ] but DA agonists also have many side effects. For example, high doses of dopaminergic agonists can result in visual hallucinations that are dose-related [ 74 ]. Pramipexole has a higher risk of ICD compared to other DA agonists due to its affinity for the D3 receptor [ 74 ].…”

“…For example, high doses of dopaminergic agonists can result in visual hallucinations that are dose-related [ 74 ]. Pramipexole has a higher risk of ICD compared to other DA agonists due to its affinity for the D3 receptor [ 74 ]. In PD patients with older ages, cognitive dysfunction and ICD, some studies suggest that DA agonists should be avoided and only levodopa is recommended; while other recent studies published found DA agonists such as Rotigotine are safe in these patients, and they can bring greater motor and non-motor benefits at the same time [ 72 , 75 ].…”

“…Its mechanism is still unclear, but seems to be related to improvement in nocturnal motor symptoms [ 109 ]. Pramipexole is reported to affect REM sleep by increasing REM sleep latency and decreasing total REM sleep time [ 74 ]. In idiopathic RBD patients, pramipexole markedly reduced the frequency and severity of RBD symptoms and maintained efficacy for up to 25 months [ 110 ] but in PD patients with RBD, pramipexol showed lack of effects [ 111 ].…”

Comparison of pramipexole and citalopram in the treatment of depression in Parkinson's disease: A randomized parallel-group trial

“…[ 17 ] Pramipexole is a nonergot dopamine agonist with a high binding specificity for the dopamine D 3 receptor subtype that is effective in the treatment of motor symptoms of PD. [ 18 19 ] Dopaminergic pathway dysfunction has been shown a role in the pathogenesis of depression. [ 20 ]…”

Untitled

“…The picture related to the nervous system does not improve immediately after lithium is discontinued. Central nervous system symptoms include a state of confusion, encephalopathy, act at the D3 subgroup level, where lithium may have no influence, and may be able to restore the balance in dopamine neurotransmission or the balance between dopamine and acetylcholine [10].…”