PRAMIPEXOLE DIHYDROCHLORIDE ANHYDROUS

First approved in 1997

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H17N3S.2ClH
Molecular Weight	284.249
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of PRAMIPEXOLE DIHYDROCHLORIDE ANHYDROUS

Structure Search

SMILES

Cl.Cl.CCCN[C@H]1CCC2=C(C1)SC(N)=N2

InChI

InChIKey=QMNWXHSYPXQFSK-KLXURFKVSA-N

InChI=1S/C10H17N3S.2ClH/c1-2-5-12-7-3-4-8-9(6-7)14-10(11)13-8;;/h7,12H,2-6H2,1H3,(H2,11,13);2*1H/t7-;;/m0../s1

HIDE SMILES / InChI

Description
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	Potency
Dopamine D3 receptor 91 Target ID: CHEMBL234 Sources: http://www.drugbank.ca/drugs/DB00413	Agonist 2678	1.5 nM [EC50]
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: http://www.drugbank.ca/drugs/DB00413	Agonist 2678	27.0 nM [EC50]
Dopamine D4 receptor 71 Target ID: CHEMBL219 Sources: http://www.drugbank.ca/drugs/DB00413	Agonist 2678	15.0 nM [EC50]
Carbonic anhydrase II 88 Target ID: CHEMBL205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24289818	Inhibitor 8297	4.81 µM [IC50]
Carbonic anhydrase I 62 Target ID: CHEMBL261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24289818	Inhibitor 8297	5.37 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Idiopathic Parkinson's disease 19 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020667s014s017s018lbl.pdf	Primary		Approved 8429	MIRAPEX Approved Use Mirapex® (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 Date 1997
Restless legs syndrome 16 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020667s014s017s018lbl.pdf	Primary		Approved 8429	MIRAPEX Approved Use Mirapex® (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 Date 1997

C_max

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

T_1/2

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 (max) Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24834511 Page: p.740	unhealthy, 61.6 n = 391 Health Status: unhealthy Condition: Parkinson's disease Age Group: 61.6 Sex: M+F Population Size: 391 Sources: https://pubmed.ncbi.nlm.nih.gov/24834511 Page: p.740	Disc. AE: Hallucination, Hypotension... AEs leading to discontinuation/dose reduction: Hallucination (1.3%) Hypotension (0.5%) Peripheral edema (0.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/24834511 Page: p.740
1.5 mg 3 times / day multiple, oral (max) Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9305331 Page: p.727	unhealthy, 62.7 n = 163 Health Status: unhealthy Condition: Parkinson's disease Age Group: 62.7 Sex: M+F Population Size: 163 Sources: https://pubmed.ncbi.nlm.nih.gov/9305331 Page: p.727	Disc. AE: Hallucinations, Sleepiness... AEs leading to discontinuation/dose reduction: Hallucinations (4.3%) Sleepiness (3%) Dizziness (2.5%) Memory loss (1.2%) Paranoia (0.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/9305331 Page: p.727
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: https://pubmed.ncbi.nlm.nih.gov/9214527 Page: p.128	unhealthy, 62.8 n = 55 Health Status: unhealthy Condition: Parkinson's disease Age Group: 62.8 Sex: M+F Population Size: 55 Sources: https://pubmed.ncbi.nlm.nih.gov/9214527 Page: p.128	DLT: Drowsiness, Muscle spasms... Dose limiting toxicities: Drowsiness (3.6%) Muscle spasms (1.8%) Insomnia (1.8%) Vertigo (1.8%) Ankle swelling (1.8%) Hallucination (3.6%) Nausea (1.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/9214527 Page: p.128
1.5 mg 3 times / day multiple, oral (max) Recommended Dose: 1.5 mg, 3 times / day Route: oral Route: multiple Dose: 1.5 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24834511 Page: p.740	unhealthy, 63 n = 511 Health Status: unhealthy Condition: Parkinson's disease Age Group: 63 Sex: M+F Population Size: 511 Sources: https://pubmed.ncbi.nlm.nih.gov/24834511 Page: p.740	Disc. AE: Nausea, Hallucination... AEs leading to discontinuation/dose reduction: Nausea (0.6%) Hallucination (1%) Peripheral edema (0.8%) Abdominal pain upper (0.6%) Myocardial infarction (0.6%) Pneumonia (0.6%) Vomiting (0.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/24834511 Page: p.740

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8356	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8356
ChemicalBook	CB0486178	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0486178
MolPort	MolPort-003-849-957	https://www.molport.com/shop/molecule-link/MolPort-003-849-957
Selleck Chemicals	Pramipexole-Mirapex	http://www.selleckchem.com/products/Pramipexole-Mirapex.html
ZINC	ZINC000003781664	http://zinc15.docking.org/substances/ZINC000003781664
eMolecules	6843675	https://www.emolecules.com/cgi-bin/more?vid=6843675

PubMed

Title	Date	PubMed
Are dopamine receptor agonists neuroprotective in Parkinson's disease?	2001	11419913
Switching from pergolide to pramipexole in patients with Parkinson's disease.	2001	11261747
Release and aggregation of cytochrome c and alpha-synuclein are inhibited by the antiparkinsonian drugs, talipexole and pramipexole.	2001 Apr 6	11301060
Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD.	2001 Jun 12	11402115
Antagonism of the discriminative stimulus effects of (+)-7-OH-DPAT by remoxipride but not PNU-99194A.	2001 Mar	11325388
Sleep disorders in Parkinson's disease: epidemiology and management.	2002	12390050
'Sleep attacks' or 'unintended sleep episodes' occur with dopamine agonists: is this a class effect?	2002	12093305
Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression.	2002 Apr 3	11926889
[Rhabdomyolysis as a complication of Parkinson's disease].	2002 Jan-Feb	12165940
Pramipexole ameliorates neurologic and psychiatric symptoms in a Westphal variant of Huntington's disease.	2002 Jan-Feb	11852299
Pramipexole in patients with Parkinson's disease and marked drug resistant tremor: a randomised, double blind, placebo controlled multicentre study.	2002 Jun	12023411
Sleep attacks in patients taking dopamine agonists: review.	2002 Jun 22	12077032
A case of Parkinsonism due to lithium intoxication: treatment with Pramipexole.	2002 May	12093142
Restless legs syndrome augmentation and pramipexole treatment.	2002 Nov	14592163
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.	2002 Nov	12388666
Neuroprotection in idiopathic Parkinson's disease.	2002 Oct	12522567
Pramipexole in Parkinson's disease. A short-term study using the combined levodopa-dopamine agonist test.	2002 Oct-Dec	12675263
Pramipexole in routine clinical practice: a prospective observational trial in Parkinson's disease.	2003	14533946
Cabergoline, pramipexole and ropinirole used as monotherapy in early Parkinson's disease: an evidence-based comparison.	2003	12964891
Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease: a meta-analysis.	2003	12688834
Dopamine agonists induce episodes of irresistible daytime sleepiness.	2003	12464715
Pramipexole in comparison to l-dopa: a neuropsychological study.	2003 Apr	12658365
Piribedil-induced sleep attacks in Parkinson's disease.	2003 Feb	12588638
Sleepwalking and sleep terrors in prepubertal children: what triggers them?	2003 Jan	12509590
Dual dopamine agonist treatment in Parkinson's disease.	2003 Jul	12883924
Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum.	2003 Oct	14523624
Current treatment options for restless legs syndrome.	2003 Oct	14521483

Patents

Sample Use Guides

In Vivo Use Guide

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

Pramipexole suppressed H2O2-induced ARPE-19 cell death in vitro at concentrations of 10(-6) M or higher.

Name

Type

Language

PRAMIPEXOLE DIHYDROCHLORIDE ANHYDROUS

Common Name

English

Pramipexole dihydrochloride [WHO-DD]

Common Name

English

ANHYDROUS PRAMIPEXOLE HYDROCHLORIDE

Common Name

English

2,6-BENZOTHIAZOLEDIAMINE, 4,5,6,7-TETRAHYDRO-N6-PROPYL-, HYDROCHLORIDE (1:2), (6S)-

Common Name

English

PRAMIPEXOLE DIHYDROCHLORIDE ANHYDROUS [MI]

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID90146623