Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C10H17N3S |
Molecular Weight | 211.327 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCN[C@H]1CCC2=C(C1)SC(N)=N2
InChI
InChIKey=FASDKYOPVNHBLU-ZETCQYMHSA-N
InChI=1S/C10H17N3S/c1-2-5-12-7-3-4-8-9(6-7)14-10(11)13-8/h7,12H,2-6H2,1H3,(H2,11,13)/t7-/m0/s1
DescriptionSources: http://www.drugbank.ca/drugs/DB00413Curator's Comment: Description was created based on several sources, including
https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020667s014s017s018lbl.pdf
Sources: http://www.drugbank.ca/drugs/DB00413
Curator's Comment: Description was created based on several sources, including
https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020667s014s017s018lbl.pdf
Pramipexole is a nonergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes. The relevance of D3 receptor binding in Parkinson's disease is unknown. The precise mechanism of action of Pramipexole as a treatment for Parkinson's disease is unknown, although it is believed to be related to its ability to stimulate dopamine receptors in the striatum. This conclusion is supported by electrophysiologic studies in animals that have demonstrated that Pramipexole influences striatal neuronal firing rates via activation of dopamine receptors in the striatum and the substantia nigra, the site of neurons that send projections to the striatum.
Pramipexole is used for the treatment of signs and symptoms of idiopathic Parkinson's disease.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL234 Sources: http://www.drugbank.ca/drugs/DB00413 |
1.5 nM [EC50] | ||
Target ID: CHEMBL217 Sources: http://www.drugbank.ca/drugs/DB00413 |
27.0 nM [EC50] | ||
Target ID: CHEMBL219 Sources: http://www.drugbank.ca/drugs/DB00413 |
15.0 nM [EC50] | ||
Target ID: CHEMBL205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24289818 |
4.81 µM [IC50] | ||
Target ID: CHEMBL261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24289818 |
5.37 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | MIRAPEX Approved UseMirapex® (pramipexole dihydrochloride) tablets are indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease.
MIRAPEX tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS). Launch Date1997 |
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Primary | MIRAPEX Approved UseMirapex® (pramipexole dihydrochloride) tablets are indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease.
MIRAPEX tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS). Launch Date1997 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.268 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20110012 |
0.375 mg single, oral dose: 0.375 mg route of administration: Oral experiment type: SINGLE co-administered: |
PRAMIPEXOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.29 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20110012 |
0.375 mg single, oral dose: 0.375 mg route of administration: Oral experiment type: SINGLE co-administered: |
PRAMIPEXOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
31.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20110012 |
0.375 mg single, oral dose: 0.375 mg route of administration: Oral experiment type: SINGLE co-administered: |
PRAMIPEXOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 61.6 |
Disc. AE: Hallucination, Hypotension... AEs leading to discontinuation/dose reduction: Hallucination (1.3%) Sources: Hypotension (0.5%) Peripheral edema (0.5%) |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 62.7 |
Disc. AE: Hallucinations, Sleepiness... AEs leading to discontinuation/dose reduction: Hallucinations (4.3%) Sources: Sleepiness (3%) Dizziness (2.5%) Memory loss (1.2%) Paranoia (0.6%) |
2 mg 3 times / day multiple, oral Highest studied dose Dose: 2 mg, 3 times / day Route: oral Route: multiple Dose: 2 mg, 3 times / day Sources: |
unhealthy, 62.8 |
DLT: Drowsiness, Muscle spasms... Dose limiting toxicities: Drowsiness (3.6%) Sources: Muscle spasms (1.8%) Insomnia (1.8%) Vertigo (1.8%) Ankle swelling (1.8%) Hallucination (3.6%) Nausea (1.8%) |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 63 |
Disc. AE: Hallucination, Peripheral edema... AEs leading to discontinuation/dose reduction: Hallucination (1%) Sources: Peripheral edema (0.8%) Abdominal pain upper (0.6%) Myocardial infarction (0.6%) Nausea (0.6%) Pneumonia (0.6%) Vomiting (0.6%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypotension | 0.5% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 61.6 |
Peripheral edema | 0.5% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 61.6 |
Hallucination | 1.3% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 61.6 |
Paranoia | 0.6% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 62.7 |
Memory loss | 1.2% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 62.7 |
Dizziness | 2.5% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 62.7 |
Sleepiness | 3% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 62.7 |
Hallucinations | 4.3% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 62.7 |
Ankle swelling | 1.8% DLT |
2 mg 3 times / day multiple, oral Highest studied dose Dose: 2 mg, 3 times / day Route: oral Route: multiple Dose: 2 mg, 3 times / day Sources: |
unhealthy, 62.8 |
Insomnia | 1.8% DLT |
2 mg 3 times / day multiple, oral Highest studied dose Dose: 2 mg, 3 times / day Route: oral Route: multiple Dose: 2 mg, 3 times / day Sources: |
unhealthy, 62.8 |
Muscle spasms | 1.8% DLT |
2 mg 3 times / day multiple, oral Highest studied dose Dose: 2 mg, 3 times / day Route: oral Route: multiple Dose: 2 mg, 3 times / day Sources: |
unhealthy, 62.8 |
Nausea | 1.8% DLT |
2 mg 3 times / day multiple, oral Highest studied dose Dose: 2 mg, 3 times / day Route: oral Route: multiple Dose: 2 mg, 3 times / day Sources: |
unhealthy, 62.8 |
Vertigo | 1.8% DLT |
2 mg 3 times / day multiple, oral Highest studied dose Dose: 2 mg, 3 times / day Route: oral Route: multiple Dose: 2 mg, 3 times / day Sources: |
unhealthy, 62.8 |
Drowsiness | 3.6% DLT |
2 mg 3 times / day multiple, oral Highest studied dose Dose: 2 mg, 3 times / day Route: oral Route: multiple Dose: 2 mg, 3 times / day Sources: |
unhealthy, 62.8 |
Hallucination | 3.6% DLT |
2 mg 3 times / day multiple, oral Highest studied dose Dose: 2 mg, 3 times / day Route: oral Route: multiple Dose: 2 mg, 3 times / day Sources: |
unhealthy, 62.8 |
Abdominal pain upper | 0.6% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 63 |
Myocardial infarction | 0.6% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 63 |
Nausea | 0.6% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 63 |
Pneumonia | 0.6% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 63 |
Vomiting | 0.6% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 63 |
Peripheral edema | 0.8% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 63 |
Hallucination | 1% Disc. AE |
1.5 mg 3 times / day multiple, oral Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: |
unhealthy, 63 |
PubMed
Title | Date | PubMed |
---|---|---|
Efficacy of pramipexole, a new dopamine receptor agonist, to relieve the parkinsonian-like muscle rigidity in rats. | 1999 Nov 26 |
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Pramipexole-induced somnolence and episodes of daytime sleep. | 2000 Jul |
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Increased risk of somnolence with the new dopamine agonists in patients with Parkinson's disease: a meta-analysis of randomised controlled trials. | 2001 |
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Economic and health-related quality of life considerations of new therapies in Parkinson's disease. | 2001 |
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Sleep disorders in patients with Parkinson's disease: epidemiology and management. | 2001 |
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Adjunctive dopamine agonists in treatment-resistant bipolar II depression: an open case series. | 2001 Jul |
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Pramipexole augmentation in panic with agoraphobia. | 2001 Mar |
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Daytime sleepiness and other sleep disorders in Parkinson's disease. | 2001 Oct 23 |
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Choosing the right dopamine agonist for patients with Parkinson's disease. | 2002 |
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'Sleep attacks' or 'unintended sleep episodes' occur with dopamine agonists: is this a class effect? | 2002 |
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Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. | 2002 Apr 3 |
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Pramipexole for depression. | 2002 Feb |
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Inhibition by R(+) or S(-) pramipexole of caspase activation and cell death induced by methylpyridinium ion or beta amyloid peptide in SH-SY5Y neuroblastoma. | 2002 Feb 15 |
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Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group. | 2002 Jan 23-30 |
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[Rhabdomyolysis as a complication of Parkinson's disease]. | 2002 Jan-Feb |
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Pramipexole ameliorates neurologic and psychiatric symptoms in a Westphal variant of Huntington's disease. | 2002 Jan-Feb |
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Pramipexole in patients with Parkinson's disease and marked drug resistant tremor: a randomised, double blind, placebo controlled multicentre study. | 2002 Jun |
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[Multiple latency test in a patient with episodes of sleep induced by pergolide]. | 2002 Jun 16-30 |
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Sleep attacks in patients taking dopamine agonists: review. | 2002 Jun 22 |
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A case of Parkinsonism due to lithium intoxication: treatment with Pramipexole. | 2002 May |
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Pramipexole in Parkinson's disease. A short-term study using the combined levodopa-dopamine agonist test. | 2002 Oct-Dec |
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Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease: a meta-analysis. | 2003 |
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Pramipexole in comparison to l-dopa: a neuropsychological study. | 2003 Apr |
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Piribedil-induced sleep attacks in Parkinson's disease. | 2003 Feb |
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Double-blind, single-dose, cross-over study of the effects of pramipexole, pergolide, and placebo on rest tremor and UPDRS part III in Parkinson's disease. | 2003 Feb |
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Slowing Parkinson's disease progression: recent dopamine agonist trials. | 2003 Feb 11 |
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Efficacy, safety and cost of new drugs acting on the central nervous system. | 2003 May |
|
Dihydroergocriptine in Parkinson's disease: clinical efficacy and comparison with other dopamine agonists. | 2003 May |
Sample Use Guides
Dosages should be increased gradually from a starting dose of 0.375 mg/day given in three divided doses and should not be increased more frequently than every 5 to 7 days.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26213307
Pramipexole suppressed H2O2-induced ARPE-19 cell death in vitro at concentrations of 10(-6) M or higher.
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Classification Tree | Code System | Code | ||
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WHO-VATC |
QN04BC05
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LIVERTOX |
NBK547968
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NDF-RT |
N0000000117
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FDA ORPHAN DRUG |
252007
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NCI_THESAURUS |
C265
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WHO-ATC |
N04BC05
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NDF-RT |
N0000175768
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100000085495
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119570
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760426
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DB00413
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104632-26-0
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PRAMIPEXOLE
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2233
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83619PEU5T
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C66456
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HH-63
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746741
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Pramipexole
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DTXSID6023496
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953
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83619PEU5T
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6227
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8253
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8356
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C061333
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m9095
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SUB09990MIG
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CHEMBL301265
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)