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Identification
NamePramipexole
Accession NumberDB00413  (APRD00156)
Typesmall molecule
Groupsapproved, investigational
Description

Pramipexole 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 bipolar disorder. Pramipexole is classified as a non-ergoline dopamine agonist.

Structure
Thumb
Synonyms
SynonymLanguageCode
(-)-PramipexoleNot AvailableNot Available
(S)-Nā€Šā€Š6-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamineNot AvailableIUPAC
2,6-Benzothiazolediamine, 4,5,6,7-tetrahydro-N(sup 6)-propyl-, (S)-Not AvailableNot Available
PramipexolGerman/SpanishNot Available
PramipexoleNot AvailableDCF, USAN, BAN
PramipexolumLatinINN
Salts
Name/CAS Structure Properties
Pramipexole hydrochloride
104632-25-9
Thumb
  • InChI Key: QMNWXHSYPXQFSK-KLXURFKVSA-N
  • Monoisotopic Mass: 283.067673727
  • Average Mass: 284.249
DBSALT000143
Brand names
NameCompany
GleparkGlenmark
MedopexolMedochemie
MiramelClonmel
MiraperSpecifar
MirapexBoehringer Ingelheim
MirapexinBoehringer Ingelheim
PexolaBoehringer Ingelheim
SifrolBoehringer Ingelheim
Sifrol ERBoehringer Ingelheim
Brand mixturesNot Available
Categories
CAS number104632-26-0
WeightAverage: 211.327
Monoisotopic: 211.114318249
Chemical FormulaC10H17N3S
InChI KeyFASDKYOPVNHBLU-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)-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine
SMILES
CCCN[C@H]1CCC2=C(C1)SC(N)=N2
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassAzoles
SubclassThiazoles
Direct parentAminothiazoles
Alternative parentsPrimary Aromatic Amines; Polyamines; Dialkylamines
Substituentspolyamine; secondary aliphatic amine; secondary amine; primary amine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the aminothiazoles. These are compounds containing a thiazole ring substituted by one or more amine groups.
Pharmacology
IndicationFor the treatment of signs and symptoms of idiopathic Parkinson's disease
PharmacodynamicsPramipexole 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.
Mechanism of actionThe 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.
AbsorptionRapid. Absolute bioavailability is greater than 90%, indicating that pramipexole is well absorbed and undergoes little presystemic metabolism. Food does not affect the extent of absorption.
Volume of distribution
  • 500 L
Protein bindingAbout 15% bound to plasma proteins.
Metabolism

No metabolites have been identified in plasma or urine.

Route of eliminationUrinary excretion is the major route of pramipexole elimination, with 90% of a pramipexole dose recovered in urine, almost all as unchanged drug. Nonrenal routes may contribute to a small extent to pramipexole elimination, although no metabolites have been identified in plasma or urine.
Half life8 hours
Clearance
  • renal cl=400 mL/min
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrate Non-inhibitor 0.7353
CYP450 2D6 substrate Inhibitor 0.5364
CYP450 2C19 substrate Inhibitor 0.586
CYP450 3A4 substrate 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
Pharmacoeconomics
Manufacturers
  • Boehringer ingelheim
Packagers
Dosage forms
FormRouteStrength
TabletOral0.125 mg
TabletOral0.25 mg
TabletOral0.5 mg
TabletOral1 mg
TabletOral1.5 mg
Prices
Unit descriptionCostUnit
Mirapex er 0.375 mg tablet9.83USDtablet
Mirapex er 0.75 mg tablet9.83USDtablet
Mirapex er 1.5 mg tablet9.83USDtablet
Mirapex er 3 mg tablet9.83USDtablet
Mirapex er 4.5 mg tablet9.83USDtablet
Mirapex 0.125 mg tablet3.48USDtablet
Mirapex 0.25 mg tablet3.42USDtablet
Mirapex 0.5 mg tablet3.42USDtablet
Mirapex 1 mg tablet3.42USDtablet
Mirapex 1.5 mg tablet3.42USDtablet
Mirapex 0.75 mg tablet3.28USDtablet
Pramipexole Dihydrochloride 0.125 mg tablet3.07USDtablet
Pramipexole Dihydrochloride 0.25 mg tablet3.07USDtablet
Pramipexole Dihydrochloride 0.5 mg tablet3.07USDtablet
Pramipexole Dihydrochloride 1 mg tablet3.07USDtablet
Pramipexole Dihydrochloride 1.5 mg tablet3.07USDtablet
Pramipexole di-hcl 0.125 mg tablet2.95USDtablet
Pramipexole di-hcl 0.25 mg tablet2.95USDtablet
Pramipexole di-hcl 0.5 mg tablet2.95USDtablet
Pramipexole di-hcl 1 mg tablet2.95USDtablet
Pramipexole di-hcl 1.5 mg tablet2.95USDtablet
Mirapex 1 mg Tablet2.2USDtablet
Mirapex 1.5 mg Tablet2.2USDtablet
Apo-Pramipexole 1 mg Tablet1.23USDtablet
Apo-Pramipexole 1.5 mg Tablet1.23USDtablet
Co Pramipexole 1 mg Tablet1.23USDtablet
Co Pramipexole 1.5 mg Tablet1.23USDtablet
Novo-Pramipexole 1 mg Tablet1.23USDtablet
Novo-Pramipexole 1.5 mg Tablet1.23USDtablet
Pms-Pramipexole 1 mg Tablet1.23USDtablet
Pms-Pramipexole 1.5 mg Tablet1.23USDtablet
Sandoz Pramipexole 1 mg Tablet1.23USDtablet
Sandoz Pramipexole 1.5 mg Tablet1.23USDtablet
Mirapex 0.25 mg Tablet1.1USDtablet
Apo-Pramipexole 0.25 mg Tablet0.62USDtablet
Co Pramipexole 0.25 mg Tablet0.62USDtablet
Novo-Pramipexole 0.25 mg Tablet0.62USDtablet
Pms-Pramipexole 0.25 mg Tablet0.62USDtablet
Sandoz Pramipexole 0.25 mg Tablet0.62USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States60018611998-01-162018-01-16
United States48868121993-10-082010-10-08
Canada22753792006-11-282018-01-16
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP0.4Not Available
Predicted Properties
PropertyValueSource
water solubility1.40e-01 g/lALOGPS
logP2.18ALOGPS
logP1.76ChemAxon
logS-3.2ALOGPS
pKa (strongest acidic)17.66ChemAxon
pKa (strongest basic)10.31ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count2ChemAxon
polar surface area50.94ChemAxon
rotatable bond count3ChemAxon
refractivity59.77ChemAxon
polarizability24.47ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US4886812
General Reference
  1. 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. Pubmed
External Links
ResourceLink
KEGG DrugD00559
BindingDB50226040
ChEBI8356
ChEMBLCHEMBL301265
Therapeutic Targets DatabaseDAP000019
PharmGKBPA164742949
IUPHAR953
Guide to Pharmacology953
Drug Product Database2241594
RxListhttp://www.rxlist.com/cgi/generic/prampex.htm
Drugs.comhttp://www.drugs.com/cdi/pramipexole.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/mir1271.shtml
WikipediaPramipexole
ATC CodesN04BC05
AHFS Codes
  • 28:36.20.08
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
CimetidineCimetidine may increase the effect and toxicity of pramipexole.
DihydrocodeineDihydrocodeine may enhance the sedative effect of pramipexole. It is recommended to monitor therapy
PaliperidoneThe atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, pramipexole. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.
ThiothixeneThiothixene may antaonize the effects of the anti-Parkinsonian agent, Pramipexole. Consider alternate therapy or monitor for decreased effects of both agents.
TriprolidineThe CNS depressants, Triprolidine and Pramipexole, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
ZiprasidoneThe atypical antipsychotic, ziprasidone, may antagonize the effect of the dopamine agonist, pramipexole. Consider alternate therapy or monitor for worsening of movement disorder.
ZuclopenthixolAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and pramipexole, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
Zuclopenthixol acetateAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and pramipexole, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
Zuclopenthixol decanoateAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and pramipexole, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
Food Interactions
  • Take without regard to meals, however if nausea is a problem, taking the product with food may reduce its incidence.

Targets

1. D(3) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
D(3) dopamine receptor P35462 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

2. D(2) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
D(2) dopamine receptor P14416 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  3. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

3. D(4) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
D(4) dopamine receptor P21917 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

4. Alpha-2B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
Alpha-2B adrenergic receptor P18089 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

5. 5-hydroxytryptamine receptor 1A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1A P08908 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

6. 5-hydroxytryptamine receptor 1D

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1D P28221 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

7. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: partial agonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

8. 5-hydroxytryptamine receptor 1B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1B P28222 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

9. 5-hydroxytryptamine receptor 2A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

10. 5-hydroxytryptamine receptor 2B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2B P41595 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

11. 5-hydroxytryptamine receptor 2C

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2C P28335 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

12. Alpha-2C adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
Alpha-2C adrenergic receptor P18825 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  2. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

13. D(1A) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
D(1A) dopamine receptor P21728 Details

References:

  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

14. D(1B) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
D(1B) dopamine receptor P21918 Details

References:

  1. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

Transporters

1. Solute carrier family 22 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

References:

  1. 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. Pubmed

2. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

References:

  1. 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. Pubmed

Comments
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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:25