Pramipexole

Identification

Summary

Pramipexole is a non-ergot dopamine agonist used to treat the signs and symptoms of idiopathic Parkinson's disease and Restless Legs Syndrome (RLS).

Brand Names

Mirapex, Mirapexin, Sifrol

Generic Name

Pramipexole

DrugBank Accession Number

DB00413

Background

Pramipexole is a drug used to treat the symptoms of Parkinson's Disease (PD). It is a non-ergot dopamine agonist drug that is efficacious in treating various Parkinson's symptoms such as tremor, rigidity, and bradykinesia (slow movement) ⁶. It was first approved by the FDA in 1997 ¹². Parkinson's Disease is one of the most common neurodegenerative disorders and causes a high level of disability in patients ², leading to increased difficulty in performing activities of daily living due to symptoms that progress over time ³. The prevalence of Parkinson's Disease worldwide has increased from approximately 2.5 million in 1990 to about 6.1 million in 2016 ⁴. This increase may be attributed to an aging population along with other contributing factors ⁴.

In addition to the above FDA approval for Parkinson's Disease, pramipexole was also approved by the FDA in 2006 for the treatment of Restless Legs Syndrome (RLS) ⁸. RLS is a sleep-related disorder characterized by unpleasant sensations in the lower extremities, often accompanied by an uncontrollable urge to move the legs ⁹.

Type

Small Molecule

Groups

Approved, Investigational

Structure

Similar Structures

Weight: Average: 211.327
Monoisotopic: 211.114318249
Chemical Formula: C₁₀H₁₇N₃S

Synonyms

(-)-Pramipexole
(S)-N 6-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine
Pramipexol
Pramipexole
Pramipexolum

External IDs

PNU 98528
SND 919 Cl 2Y
SUD 919 CL 24
U 98528 E

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Pharmacology

Indication

This drug is indicated for the symptomatic treatment of Parkinson’s disease ^Label. This drug can be administered as monotherapy or in conjunction with levodopa. It is also indicated for symptomatic treatment of moderate to severe primary Restless Legs Syndrome (RLS) ^Label.

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Associated Conditions

Indication Type	Indication	Approval Level	Dose Form
Treatment of	Moderate restless legs syndrome (rls)	••••••••••••	••••••
Symptomatic treatment of	Parkinson's disease	••••••••••••	••••••
Treatment of	Severe restless legs syndrome (rls)	••••••••••••	••••••

Contraindications & Blackbox Warnings

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Pharmacodynamics

Parkinson's Disease

Through the stimulation of dopamine receptors, pramipexole is thought to relieve the symptoms of Parkinson's Disease ^Label. The motor symptoms of Parkinson's disease occur partly due to a reduction of dopamine in the substantia nigra of the brain ¹¹. Dopamine is an essential neurotransmitter that has major effects on motor movements in humans.

Restless Legs Syndrome

Pramipexole likely restores balance to the dopaminergic system, controlling the symptoms of this condition. Restless legs syndrome is thought to occur, in part, through dysfunction of the dopaminergic system, resulting in unpleasant lower extremity symptoms ⁹, ¹⁵.

Other effects

In addition to the abovementioned effects, animal studies demonstrate that pramipexole blocks dopamine synthesis, release, and turnover. Additionally, this drug is neuroprotective to dopamine neuron degeneration after ischemia or methamphetamine neurotoxicity ¹⁵.

Mechanism of action

The exact mechanism of action of pramipexole as a treatment for Parkinson's disease is unknown at this time. It is thought, however, that the ability of pramipexole to cause stimulation of the dopamine receptors in the striatum of the brain, a region that receives a vast array of neurological input and is responsible for a wide variety of functions, may be involved¹⁰. Studies performed in animals show that pramipexole influences striatal neuronal transmission rates following activation of dopamine receptors ^Label.

Pramipexole is considered a non-ergot dopamine agonist that shows specificity and strong activity at the D2 subfamily of dopamine receptors in vitro, binding selectively and dopamine D2 receptors and showing a preference for the dopamine D3 receptor subtype rather than other subtypes ⁸. The clinical significance of this binding specificity is unknown ^Label, ⁸.

Target	Actions	Organism
ADopamine D3 receptor	agonist	Humans
ADopamine D2 receptor	agonist	Humans
ADopamine D4 receptor	agonist	Humans
U5-hydroxytryptamine receptor 1A	agonist	Humans
UAlpha-2A adrenergic receptor	agonist	Humans

Absorption

The bioavailability of pramipexole is higher than 90%, indicating a high level of absorption ^Label.

Volume of distribution

This drug is extensively distributed in the body with a volume of distribution of approximately 500 L ^Label.

Protein binding

About 15% bound to plasma proteins ^Label.

Metabolism

This drug undergoes little metabolism in humans ^Label.

Route of elimination

The main route of pramipexole elimination, with 90% of a pramipexole dose found in the urine, almost entirely as unchanged drug ^Label.

Half-life

About 8.5-12 hours ^Label.

Clearance

Renal clearance is about 400 mL/min, indicating heavy secretion by the renal tubules ^Label.

Adverse Effects

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Toxicity

LD50

Rat Oral LD 50 >800 mg/kg ¹⁴.

Carcinogenicity, mutagenicity, impact on fertility

Pramipexole was not found to be carcinogenic in 2-year studies on mice and rats at 0.3, 2.2, and 11 times the maximum recommended human dose (MRHD). No increased incidence of tumors was observed ^Label. No mutagenicity was detected in various assays, including the Ames test. Finally, pramipexole given to rat models at a dose of 2.5 mg/kg/day (5 times the maximum recommended human dose), increased estrus cycles and inhibited implantation of a fertilized ovum. Decreased levels of prolactin, a hormone necessary for implantation and maintenance of early pregnancy, were measured ^Label. The significance of these findings in humans is unknown.

Pregnancy

This drug is considered a pregnancy category C drug, showing teratogenic effects in animals. Currently, there no studies of pramipexole in human pregnancy. Animal reproduction studies are not always predictive of human response. This drug should only be used in pregnancy if the potential benefit outweighs the possible fetal risks ^Label.

Nursing

Whether pramipexole is excreted in human milk is unknown. A decision should be made regarding the administration pramipexole during nursing, or whether to discontinue it during nursing, as many drugs are excreted in human milk. The potential exists for risk to the infant if pramipexole is, in fact, excreted in the milk ^Label.

Pathways

Not Available

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Not Available

Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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1,2-Benzodiazepine	1,2-Benzodiazepine may increase the sedative activities of Pramipexole.
Abacavir	Pramipexole may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abaloparatide	The risk or severity of adverse effects can be increased when Pramipexole is combined with Abaloparatide.
Acebutolol	The risk or severity of adverse effects can be increased when Pramipexole is combined with Acebutolol.
Aceclofenac	Aceclofenac may decrease the excretion rate of Pramipexole which could result in a higher serum level.

Food Interactions

Take with or without food. Food decreases the risk of GI side effects.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Pramipexole dihydrochloride monohydrate	3D867NP06J	191217-81-9	APVQOOKHDZVJEX-QTPLPEIMSA-N
Pramipexole hydrochloride	4R2HD0M28N	104632-25-9	QMNWXHSYPXQFSK-KLXURFKVSA-N

Product Images

International/Other Brands

Glepark (Glenmark) / Medopexol (Medochemie) / Miramel (Clonmel) / Miraper (Specifar) / Pexola (Boehringer Ingelheim) / Sifrol ER (Boehringer Ingelheim)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Act Pramipexole	Tablet	1.5 mg	Oral	TEVA Canada Limited	2009-04-15	Not applicable
Act Pramipexole	Tablet	0.5 mg	Oral	TEVA Canada Limited	2009-04-15	Not applicable
Act Pramipexole	Tablet	1 mg	Oral	TEVA Canada Limited	2009-04-15	Not applicable
Act Pramipexole	Tablet	0.25 mg	Oral	TEVA Canada Limited	2009-04-15	Not applicable
Mirapex	Tablet	.500 mg/1	Oral	Boehringer Ingelheim Pharmaceuticals, Inc.	2004-01-01	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Apo-pramipexole	Tablet	0.75 mg	Oral	Apotex Corporation	Not applicable	Not applicable
Apo-pramipexole	Tablet	1.0 mg	Oral	Apotex Corporation	2007-02-26	Not applicable
Apo-pramipexole	Tablet	0.5 mg	Oral	Apotex Corporation	2007-02-26	Not applicable
Apo-pramipexole	Tablet	0.125 mg	Oral	Apotex Corporation	Not applicable	Not applicable
Apo-pramipexole	Tablet	1.5 mg	Oral	Apotex Corporation	2007-02-26	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Mirapex ER	Pramipexole dihydrochloride monohydrate (0.375 mg/1) + Pramipexole dihydrochloride monohydrate (0.75 mg/1) + Pramipexole dihydrochloride monohydrate (1.5 mg/1)	Kit	Oral	Boehringer Ingelheim Pharmaceuticals, Inc.	2010-02-22	2010-11-03
Mirapex ER	Pramipexole dihydrochloride monohydrate (0.375 mg/1) + Pramipexole dihydrochloride monohydrate (0.75 mg/1) + Pramipexole dihydrochloride monohydrate (1.5 mg/1)	Kit	Oral	Boehringer Ingelheim Pharmaceuticals, Inc.	2010-02-22	2010-11-03
Mirapex ER	Pramipexole dihydrochloride monohydrate (0.375 mg/1) + Pramipexole dihydrochloride monohydrate (0.75 mg/1) + Pramipexole dihydrochloride monohydrate (1.5 mg/1)	Kit	Oral	Boehringer Ingelheim Pharmaceuticals, Inc.	2010-02-22	2010-11-03
OPRYMEA	Pramipexole (0.26 MG) + Pramipexole (0.52 MG) + Pramipexole (1.05 MG)	Tablet, extended release	Oral	Krka D.D. Novo Mesto	2016-10-12	Not applicable
OPRYMEA	Pramipexole (0.26 MG) + Pramipexole (0.52 MG) + Pramipexole (1.05 MG)	Tablet, extended release	Oral	Krka D.D. Novo Mesto	2016-10-12	Not applicable

Chemical Identifiers

UNII: 83619PEU5T
CAS number: 104632-26-0
InChI Key: FASDKYOPVNHBLU-ZETCQYMHSA-N
InChI: 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
IUPAC Name: (6S)-N6-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine
SMILES: CCCN[C@H]1CCC2=C(C1)SC(N)=N2

References

Synthesis Reference

US4886812

General References

Mierau J, Schneider FJ, Ensinger HA, Chio CL, Lajiness ME, Huff RM: Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors. Eur J Pharmacol. 1995 Jun 23;290(1):29-36. [Article]
Massano J, Bhatia KP: Clinical approach to Parkinson's disease: features, diagnosis, and principles of management. Cold Spring Harb Perspect Med. 2012 Jun;2(6):a008870. doi: 10.1101/cshperspect.a008870. [Article]
Poewe W, Mahlknecht P: The clinical progression of Parkinson's disease. Parkinsonism Relat Disord. 2009 Dec;15 Suppl 4:S28-32. doi: 10.1016/S1353-8020(09)70831-4. [Article]
Authors unspecified: Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018 Nov;17(11):939-953. doi: 10.1016/S1474-4422(18)30295-3. Epub 2018 Oct 1. [Article]
Aiken CB: Pramipexole in psychiatry: a systematic review of the literature. J Clin Psychiatry. 2007 Aug;68(8):1230-6. [Article]
Constantinescu R: Update on the use of pramipexole in the treatment of Parkinson's disease. Neuropsychiatr Dis Treat. 2008 Apr;4(2):337-52. [Article]
Antonini A, Calandrella D: Pharmacokinetic evaluation of pramipexole. Expert Opin Drug Metab Toxicol. 2011 Oct;7(10):1307-14. doi: 10.1517/17425255.2011.614232. Epub 2011 Sep 6. [Article]
Merlino G, Serafini A, Robiony F, Valente M, Gigli GL: Clinical experience with pramipexole in the treatment of restless legs syndrome. Expert Opin Drug Metab Toxicol. 2008 Feb;4(2):225-35. doi: 10.1517/17425255.4.2.225. [Article]
Guo S, Huang J, Jiang H, Han C, Li J, Xu X, Zhang G, Lin Z, Xiong N, Wang T: Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management. Front Aging Neurosci. 2017 Jun 2;9:171. doi: 10.3389/fnagi.2017.00171. eCollection 2017. [Article]
Rolls ET: Neurophysiology and cognitive functions of the striatum. Rev Neurol (Paris). 1994 Aug-Sep;150(8-9):648-60. [Article]
Galvan A, Wichmann T: Pathophysiology of parkinsonism. Clin Neurophysiol. 2008 Jul;119(7):1459-74. doi: 10.1016/j.clinph.2008.03.017. Epub 2008 May 7. [Article]
FDA Approval package, Mirapex [Link]
Mirapex® (pramipexole dihydrochloride) FDA Label [Link]
Pramipexole hydrochloride tablets SDS [File]
MedSafe NZ, Ramipex tablet information sheet [File]

External Links

Human Metabolome Database: HMDB0014557
KEGG Drug: D00559
PubChem Compound: 119570
PubChem Substance: 46505897
ChemSpider: 106770
BindingDB: 50116766
RxNav: 746741
ChEBI: 8356
ChEMBL: CHEMBL301265
ZINC: ZINC000003781664
Therapeutic Targets Database: DAP000019
PharmGKB: PA164742949
Guide to Pharmacology: GtP Drug Page
PDBe Ligand: G6L
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
PDRhealth: PDRhealth Drug Page
Wikipedia: Pramipexole

PDB Entries

7cmu

FDA label

Download (353 KB)

MSDS

Download (25.4 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Diagnostic	Parkinson's Disease (PD)	1
4	Completed	Other	Major Depressive Disorder (MDD)	1
4	Completed	Other	Restless Legs Syndrome (RLS)	1
4	Completed	Treatment	Bipolar Disorder (BD)	2
4	Completed	Treatment	Depression	1

Pharmacoeconomics

Manufacturers

Boehringer ingelheim

Packagers

Barr Pharmaceuticals
Boehringer Ingelheim Ltd.
Cardinal Health
Kaiser Foundation Hospital
Murfreesboro Pharmaceutical Nursing Supply
Pfizer Inc.
Pharmacia Inc.
Physicians Total Care Inc.
Rebel Distributors Corp.
Resource Optimization and Innovation LLC
Sandoz
Stat Rx Usa
Teva Pharmaceutical Industries Ltd.
Vangard Labs Inc.
Zydus Pharmaceuticals

Dosage Forms

Form	Route	Strength
Tablet	Oral	0.75 mg
Tablet	Oral	0.26 mg
Tablet	Oral	0.52 mg
Tablet	Oral	1.05 mg
Tablet	Oral	1.57 mg
Tablet	Oral	2.1 mg
Tablet	Oral	2.62 mg
Tablet	Oral	3.15 mg
Tablet	Oral	0.088 MG
Tablet	Oral	0.18 MG
Tablet	Oral	0.35 MG
Tablet	Oral	0.7 MG
Tablet	Oral	0.250 mg
Tablet	Oral	.250 mg/1
Tablet	Oral	.500 mg/1
Tablet	Oral	.750 mg/1
Tablet	Oral	0.125 mg/1
Tablet	Oral	0.250 mg/1
Tablet	Oral	0.5 mg
Tablet	Oral	0.500 mg/1
Tablet	Oral	1.5 mg
Kit	Oral
Tablet	Oral	0.88 MG
Tablet, extended release	Oral	0.52 MG
Tablet, extended release	Oral	1.05 MG
Tablet, extended release	Oral	2.10 MG
Tablet, extended release	Oral	2.1 MG
Tablet, extended release	Oral	3.15 MG
Tablet	Oral	1.10 MG
Tablet, extended release	Oral	0.26 MG
Tablet, extended release	Oral	1.57 MG
Tablet, extended release	Oral	2.62 MG
Tablet, extended release	Oral
Tablet	Oral	0.25 mg
Tablet	Oral	1 mg
Tablet, extended release	Oral	2.25 mg
Tablet, extended release	Oral	3 mg
Tablet, extended release	Oral	3.75 mg
Tablet, extended release	Oral	4.5 mg
Tablet	Oral	0250 mg
Tablet, extended release	Oral	0750 mg
Tablet, extended release	Oral	1500 mg
Tablet, orally disintegrating	Oral
Tablet	Oral	0.50 mg
Tablet, extended release	Oral
Tablet	Oral	1.1 MG
Tablet	Oral	0.70 MG
Tablet, coated	Oral	1 mg
Tablet	Oral
Tablet	Oral	0.54 MG
Tablet	Oral	0.25 mg/1
Tablet	Oral	0.5 mg/1
Tablet	Oral	0.75 mg/1
Tablet	Oral	1 mg/1
Tablet	Oral	1.5 mg/1
Tablet, extended release	Oral	0.375 mg/1
Tablet, extended release	Oral	0.75 mg/1
Tablet, extended release	Oral	1.5 mg/1
Tablet, extended release	Oral	2.25 mg/1
Tablet, extended release	Oral	3 mg/1
Tablet, extended release	Oral	3.75 mg/1
Tablet, extended release	Oral	4.5 mg/1
Tablet	Oral	0018 MG
Tablet	Oral	0088 MG
Tablet, extended release	Oral	0375 Mg
Tablet, extended release	Oral	1.500 mg
Tablet	Oral	1.0 mg
Tablet, extended release	Oral	0.375 mg
Tablet, extended release	Oral	0.75 mg
Tablet, extended release	Oral	1.5 mg
Tablet	Oral	0.125 mg

Prices

Unit description	Cost	Unit
Mirapex er 0.375 mg tablet	9.83USD	tablet
Mirapex er 0.75 mg tablet	9.83USD	tablet
Mirapex er 1.5 mg tablet	9.83USD	tablet
Mirapex er 3 mg tablet	9.83USD	tablet
Mirapex er 4.5 mg tablet	9.83USD	tablet
Mirapex 0.125 mg tablet	3.48USD	tablet
Mirapex 0.25 mg tablet	3.42USD	tablet
Mirapex 0.5 mg tablet	3.42USD	tablet
Mirapex 1 mg tablet	3.42USD	tablet
Mirapex 1.5 mg tablet	3.42USD	tablet
Mirapex 0.75 mg tablet	3.28USD	tablet
Pramipexole Dihydrochloride 0.125 mg tablet	3.07USD	tablet
Pramipexole Dihydrochloride 0.25 mg tablet	3.07USD	tablet
Pramipexole Dihydrochloride 0.5 mg tablet	3.07USD	tablet
Pramipexole Dihydrochloride 1 mg tablet	3.07USD	tablet
Pramipexole Dihydrochloride 1.5 mg tablet	3.07USD	tablet
Pramipexole di-hcl 0.125 mg tablet	2.95USD	tablet
Pramipexole di-hcl 0.25 mg tablet	2.95USD	tablet
Pramipexole di-hcl 0.5 mg tablet	2.95USD	tablet
Pramipexole di-hcl 1 mg tablet	2.95USD	tablet
Pramipexole di-hcl 1.5 mg tablet	2.95USD	tablet
Mirapex 1 mg Tablet	2.2USD	tablet
Mirapex 1.5 mg Tablet	2.2USD	tablet
Apo-Pramipexole 1 mg Tablet	1.23USD	tablet
Apo-Pramipexole 1.5 mg Tablet	1.23USD	tablet
Co Pramipexole 1 mg Tablet	1.23USD	tablet
Co Pramipexole 1.5 mg Tablet	1.23USD	tablet
Novo-Pramipexole 1 mg Tablet	1.23USD	tablet
Novo-Pramipexole 1.5 mg Tablet	1.23USD	tablet
Pms-Pramipexole 1 mg Tablet	1.23USD	tablet
Pms-Pramipexole 1.5 mg Tablet	1.23USD	tablet
Sandoz Pramipexole 1 mg Tablet	1.23USD	tablet
Sandoz Pramipexole 1.5 mg Tablet	1.23USD	tablet
Mirapex 0.25 mg Tablet	1.1USD	tablet
Apo-Pramipexole 0.25 mg Tablet	0.62USD	tablet
Co Pramipexole 0.25 mg Tablet	0.62USD	tablet
Novo-Pramipexole 0.25 mg Tablet	0.62USD	tablet
Pms-Pramipexole 0.25 mg Tablet	0.62USD	tablet
Sandoz Pramipexole 0.25 mg Tablet	0.62USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US4886812	No	1989-12-12	2010-10-08
CA2275379	No	2006-11-28	2018-01-16
US6001861	No	1999-12-14	2018-01-16
US6194445	No	2001-02-27	2018-01-16
US8679533	No	2014-03-25	2029-09-08
US7695734	No	2010-04-13	2028-04-26

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	288-290	https://www.chemicalbook.com/ChemicalProductProperty_US_CB0486178.aspx
boiling point (°C)	378	https://www.lookchem.com/Pramipexole/
water solubility	freely soluble in water	https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022421s000ChemR.pdf
logP	1.42	https://pdf.hres.ca/dpd_pm/00043389.PDF
logS	-3.2	http://www.t3db.ca/toxins/T3D2783
pKa	5.6, 9.5	https://pdf.hres.ca/dpd_pm/00043389.PDF

Predicted Properties

Property	Value	Source
Water Solubility	0.14 mg/mL	ALOGPS
logP	2.18	ALOGPS
logP	1.76	Chemaxon
logS	-3.2	ALOGPS
pKa (Strongest Acidic)	17.66	Chemaxon
pKa (Strongest Basic)	10.31	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	3	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	50.94 Å²	Chemaxon
Rotatable Bond Count	3	Chemaxon
Refractivity	59.77 m³·mol^-1	Chemaxon
Polarizability	24.47 Å³	Chemaxon
Number of Rings	2	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9967
Blood Brain Barrier	+	0.9631
Caco-2 permeable	-	0.6419
P-glycoprotein substrate	Substrate	0.6384
P-glycoprotein inhibitor I	Non-inhibitor	0.842
P-glycoprotein inhibitor II	Non-inhibitor	0.7464
Renal organic cation transporter	Non-inhibitor	0.6788
CYP450 2C9 substrate	Non-substrate	0.8524
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Non-substrate	0.7558
CYP450 1A2 substrate	Inhibitor	0.9179
CYP450 2C9 inhibitor	Non-inhibitor	0.7353
CYP450 2D6 inhibitor	Inhibitor	0.5364
CYP450 2C19 inhibitor	Inhibitor	0.586
CYP450 3A4 inhibitor	Non-inhibitor	0.6708
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.7797
Ames test	Non AMES toxic	0.8133
Carcinogenicity	Non-carcinogens	0.915
Biodegradation	Not ready biodegradable	0.9255
Rat acute toxicity	2.8676 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.8732
hERG inhibition (predictor II)	Non-inhibitor	0.8397

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-0f89-5900000000-2f0a391f30cf7118b5c5
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-03di-0090000000-5bb3af51778261380cd5
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-03di-0390000000-f0111512206cbd0f2144
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03di-0090000000-a167e14cd813f750232a
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0fsr-1900000000-10e64efe5ca7fb35f1c6
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03di-0390000000-ad9548caaff7e77ef83e
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0007-1900000000-8a4c96caaadc9adae625
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	151.813793	predicted	DarkChem Lite v0.1.0
[M-H]-	156.82796	predicted	DeepCCS 1.0 (2019)
[M+H]+	151.548793	predicted	DarkChem Lite v0.1.0
[M+H]+	159.18597	predicted	DeepCCS 1.0 (2019)
[M+Na]+	152.263793	predicted	DarkChem Lite v0.1.0
[M+Na]+	167.05284	predicted	DeepCCS 1.0 (2019)

Targets

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Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	1.5	N/A	N/A	A28193 / A28194 / A28195
Ki (nM)	0.87	N/A	N/A	A28193
Ki (nM)	38	N/A	N/A	A28194 / A28195
Ki (nM)	0.88	N/A	N/A	A28194 / A28195

Details1. Dopamine D3 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: G-protein coupled amine receptor activity
Specific Function: Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name: DRD3
Uniprot ID: P35462
Uniprot Name: D(3) dopamine receptor
Molecular Weight: 44224.335 Da

References

Merlino G, Serafini A, Robiony F, Valente M, Gigli GL: Clinical experience with pramipexole in the treatment of restless legs syndrome. Expert Opin Drug Metab Toxicol. 2008 Feb;4(2):225-35. doi: 10.1517/17425255.4.2.225. [Article]
Piercey MF: Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease. Clin Neuropharmacol. 1998 May-Jun;21(3):141-51. [Article]
Chernoloz O, El Mansari M, Blier P: Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain. J Psychiatry Neurosci. 2012 Feb;37(2):113-21. doi: 10.1503/jpn.110038. [Article]
Dooley M, Markham A: Pramipexole. A review of its use in the management of early and advanced Parkinson's disease. Drugs Aging. 1998 Jun;12(6):495-514. doi: 10.2165/00002512-199812060-00007. [Article]

Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	5	N/A	N/A	A28192
IC 50 (nM)	>10000	N/A	N/A	A28196
Ki (nM)	40	N/A	N/A	A28193
Ki (nM)	27	N/A	N/A	A28193
Ki (nM)	6300	N/A	N/A	A28194 / A28195
Ki (nM)	21	N/A	N/A	A28194 / A28195
Ki (nM)	1900	N/A	N/A	A28194 / A28195

Details2. Dopamine D2 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: Potassium channel regulator activity
Specific Function: Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name: DRD2
Uniprot ID: P14416
Uniprot Name: D(2) dopamine receptor
Molecular Weight: 50618.91 Da

References

Piercey MF: Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease. Clin Neuropharmacol. 1998 May-Jun;21(3):141-51. [Article]
Chernoloz O, El Mansari M, Blier P: Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain. J Psychiatry Neurosci. 2012 Feb;37(2):113-21. doi: 10.1503/jpn.110038. [Article]
Dooley M, Markham A: Pramipexole. A review of its use in the management of early and advanced Parkinson's disease. Drugs Aging. 1998 Jun;12(6):495-514. doi: 10.2165/00002512-199812060-00007. [Article]

Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	15	N/A	N/A	A28193 / A28194
Ki (nM)	8.5	N/A	N/A	A28193
Ki (nM)	8.1	N/A	N/A	A28194 / A28195
Ki (nM)	130	N/A	N/A	A28194 / A28195

Details3. Dopamine D4 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: Sh3 domain binding
Specific Function: Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins ...
Gene Name: DRD4
Uniprot ID: P21917
Uniprot Name: D(4) dopamine receptor
Molecular Weight: 48359.86 Da

References

Piercey MF: Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease. Clin Neuropharmacol. 1998 May-Jun;21(3):141-51. [Article]
Dooley M, Markham A: Pramipexole. A review of its use in the management of early and advanced Parkinson's disease. Drugs Aging. 1998 Jun;12(6):495-514. doi: 10.2165/00002512-199812060-00007. [Article]
Mierau J, Schneider FJ, Ensinger HA, Chio CL, Lajiness ME, Huff RM: Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors. Eur J Pharmacol. 1995 Jun 23;290(1):29-36. [Article]

Details4. 5-hydroxytryptamine receptor 1A

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist
Curator comments: This is a potential target of Pramipexole.

General Function: Serotonin receptor activity
Specific Function: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name: HTR1A
Uniprot ID: P08908
Uniprot Name: 5-hydroxytryptamine receptor 1A
Molecular Weight: 46106.335 Da

References

Chernoloz O, El Mansari M, Blier P: Long-term administration of the dopamine D3/2 receptor agonist pramipexole increases dopamine and serotonin neurotransmission in the male rat forebrain. J Psychiatry Neurosci. 2012 Feb;37(2):113-21. doi: 10.1503/jpn.110038. [Article]
Chernoloz O, El Mansari M, Blier P: Sustained administration of pramipexole modifies the spontaneous firing of dopamine, norepinephrine, and serotonin neurons in the rat brain. Neuropsychopharmacology. 2009 Feb;34(3):651-61. doi: 10.1038/npp.2008.114. Epub 2008 Aug 6. [Article]
Rogoz Z, Skuza G: Mechanism of synergistic action following co-treatment with pramipexole and fluoxetine or sertraline in the forced swimming test in rats. Pharmacol Rep. 2006 Jul-Aug;58(4):493-500. [Article]

Details5. Alpha-2A adrenergic receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Agonist

General Function: Thioesterase binding
Specific Function: Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name: ADRA2A
Uniprot ID: P08913
Uniprot Name: Alpha-2A adrenergic receptor
Molecular Weight: 48956.275 Da

References

Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [Article]
Newman-Tancredi A, Cussac D, Audinot V, Nicolas JP, De Ceuninck F, Boutin JA, Millan MJ: Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor. J Pharmacol Exp Ther. 2002 Nov;303(2):805-14. [Article]
Apraxine M, Pasquet A, Jeanjean A: Pramipexole-Induced Reversible Heart Failure. Mov Disord Clin Pract. 2014 Oct 23;1(4):381-382. doi: 10.1002/mdc3.12096. eCollection 2014 Dec. [Article]
McCormick PN, Fletcher PJ, Wilson VS, Remington GJ: The adrenergic alpha2 antagonist atipamezole alters the behavioural effects of pramipexole and increases pramipexole concentration in blood plasma. Life Sci. 2016 Apr 15;151:300-304. doi: 10.1016/j.lfs.2016.03.017. Epub 2016 Mar 11. [Article]
Zhang Lab, University of Michigan document [Link]

Transporters

Details1. Solute carrier family 22 member 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Quaternary ammonium group transmembrane transporter activity
Specific Function: Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name: SLC22A2
Uniprot ID: O15244
Uniprot Name: Solute carrier family 22 member 2
Molecular Weight: 62579.99 Da

References

Ishiguro N, Saito A, Yokoyama K, Morikawa M, Igarashi T, Tamai I: Transport of the dopamine D2 agonist pramipexole by rat organic cation transporters OCT1 and OCT2 in kidney. Drug Metab Dispos. 2005 Apr;33(4):495-9. Epub 2005 Jan 7. [Article]
Diao L, Shu Y, Polli JE: Uptake of pramipexole by human organic cation transporters. Mol Pharm. 2010 Aug 2;7(4):1342-7. doi: 10.1021/mp100036b. [Article]
Knop J, Hoier E, Ebner T, Fromm MF, Muller F: Renal tubular secretion of pramipexole. Eur J Pharm Sci. 2015 Nov 15;79:73-8. doi: 10.1016/j.ejps.2015.09.004. Epub 2015 Sep 7. [Article]

Details2. Solute carrier family 22 member 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Secondary active organic cation transmembrane transporter activity
Specific Function: Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name: SLC22A1
Uniprot ID: O15245
Uniprot Name: Solute carrier family 22 member 1
Molecular Weight: 61153.345 Da

References

Ishiguro N, Saito A, Yokoyama K, Morikawa M, Igarashi T, Tamai I: Transport of the dopamine D2 agonist pramipexole by rat organic cation transporters OCT1 and OCT2 in kidney. Drug Metab Dispos. 2005 Apr;33(4):495-9. Epub 2005 Jan 7. [Article]
Diao L, Shu Y, Polli JE: Uptake of pramipexole by human organic cation transporters. Mol Pharm. 2010 Aug 2;7(4):1342-7. doi: 10.1021/mp100036b. [Article]
Antonini A, Calandrella D: Once-daily pramipexole for the treatment of early and advanced idiopathic Parkinson's disease: implications for patients. Neuropsychiatr Dis Treat. 2011;7:297-302. doi: 10.2147/NDT.S10097. Epub 2011 May 15. [Article]

Details3. Solute carrier family 22 member 3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Toxin transporter activity
Specific Function: Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name: SLC22A3
Uniprot ID: O75751
Uniprot Name: Solute carrier family 22 member 3
Molecular Weight: 61279.485 Da

References

Diao L, Shu Y, Polli JE: Uptake of pramipexole by human organic cation transporters. Mol Pharm. 2010 Aug 2;7(4):1342-7. doi: 10.1021/mp100036b. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55

Pramipexole

Identification

Structure for Pramipexole (DB00413)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

References

References

References

References

Transporters

References

References

References