PRAMIPEXOLE DIHYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H17N3S.2ClH.H2O
Molecular Weight	302.264
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of PRAMIPEXOLE DIHYDROCHLORIDE

Structure Search

SMILES

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

InChI

InChIKey=APVQOOKHDZVJEX-QTPLPEIMSA-N

InChI=1S/C10H17N3S.2ClH.H2O/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;1H2/t7-;;;/m0.../s1

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C10H17N3S
Molecular Weight	211.327
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 89 Target ID: CHEMBL234 Sources: http://www.drugbank.ca/drugs/DB00413	Agonist 2637	1.5 nM [EC50]
Dopamine D2 receptor 290 Target ID: CHEMBL217 Sources: http://www.drugbank.ca/drugs/DB00413	Agonist 2637	27.0 nM [EC50]
Dopamine D4 receptor 69 Target ID: CHEMBL219 Sources: http://www.drugbank.ca/drugs/DB00413	Agonist 2637	15.0 nM [EC50]
Carbonic anhydrase II 88 Target ID: CHEMBL205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24289818	Inhibitor 8146	4.81 µM [IC50]
Carbonic anhydrase I 62 Target ID: CHEMBL261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24289818	Inhibitor 8146	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 8307	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 8.6762881E11
Restless legs syndrome 16 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020667s014s017s018lbl.pdf	Primary		Approved 8307	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 8.6762881E11

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
Pramipexole treatment for cocaine cravings.	1999 Nov	10553755
Role of dopamine D3 receptors in thermoregulation: a reappraisal.	2000 Jan 17	10683862
Increased risk of somnolence with the new dopamine agonists in patients with Parkinson's disease: a meta-analysis of randomised controlled trials.	2001	11665873
Adjunctive dopamine agonists in treatment-resistant bipolar II depression: an open case series.	2001 Jul	11518474
Current and emerging treatments in Parkinson's disease.	2001 Mar	11379409
Newer dopamine agonists in the treatment of restless legs syndrome.	2001 May	11346069
DA agonists -- non-ergot derivatives: pramipexole: management of Parkinson's disease.	2002	12211148
Acute placebo-controlled sleep laboratory studies and clinical follow-up with pramipexole in restless legs syndrome.	2002 Aug	12242580
Gender and pramipexole effects on levodopa pharmacokinetics and pharmacodynamics.	2002 Dec 24	12499509
A review of pramipexole and its clinical utility in Parkinson's disease.	2002 Feb	11829733
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	11835316
Neuroprotection and dopamine agonists.	2002 Feb 26	11909981
Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group.	2002 Jan 23-30	11798367
Pergolide in the treatment of patients with early and advanced Parkinson's disease.	2002 Jan-Feb	11852289
Pramipexole in patients with Parkinson's disease and marked drug resistant tremor: a randomised, double blind, placebo controlled multicentre study.	2002 Jun	12023411
A case of Parkinsonism due to lithium intoxication: treatment with Pramipexole.	2002 May	12093142
Restless legs syndrome augmentation and pramipexole treatment.	2002 Nov	14592163
Dopamine agonists and neuroprotection in Parkinson's disease.	2002 Nov	12464116
Effect of daily dosing duration of direct and indirect dopamine receptor agonists: cocaine cross-tolerance following chronic regimens.	2002 Oct	12208558
Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease: a meta-analysis.	2003	12688834
Sleepwalking and sleep terrors in prepubertal children: what triggers them?	2003 Jan	12509590
Assessment of sleepiness and unintended sleep in Parkinson's disease patients taking dopamine agonists.	2003 Jul	14592299
Parkinson's disease: is the initial treatment established?	2003 Jul	12930698
Dihydroergocriptine in Parkinson's disease: clinical efficacy and comparison with other dopamine agonists.	2003 May	12713527
Potent activation of dopamine D3/D2 heterodimers by the antiparkinsonian agents, S32504, pramipexole and ropinirole.	2003 Nov	14535946
Randomized, double-blind study of pramipexole with placebo and bromocriptine in advanced Parkinson's disease.	2003 Oct	14534919

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 17:16:33 UTC 2022` Edited by `admin` on `Fri Dec 16 17:16:33 UTC 2022`
Record UNII	3D867NP06J
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PRAMIPEXOLE DIHYDROCHLORIDE

Official Name

English

SND-919CL2Y

Code

English

SND919CL2Y

Code

English

SIFROL

Brand Name

English

PRAMIPEXOLE HYDROCHLORIDE MONOHYDRATE

Common Name

English

PRAMIPEXOLE TEVA

Brand Name

English

PRAMIPEXOLE DIHYDROCHLORIDE MONOHYDRATE

Common Name

English

PRAMIPEXOLE DIHYDROCHLORIDE MONOHYDRATE [EMA EPAR]

Common Name

English

PNU-98528E

Code

English

PRAMIPEXOLE DIHYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

(S)-2-Amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole dihydrochloride monohydrate

Systematic Name

English

MIRAPEX

Brand Name

English

PRAMIPEXOLE DIHYDROCHLORIDE [VANDF]

Common Name

English

PRAMIPEXOLE ACCORD

Brand Name

English

MIRAPEXIN

Brand Name

English

PRAMIPEXOLE DIHYDROCHLORIDE MONOHYDRATE [USP-RS]

Common Name

English

PRAMIPEXOLE HYDROCHLORIDE HYDRATE [JAN]

Common Name

English

PRAMIPEXOLE DIHYDROCHLORIDE [USAN]

Common Name

English

PRAMIPEXOLE HYDROCHLORIDE [MART.]

Common Name

English

PRAMIPEXOLE DIHYDROCHLORIDE MONOHYDRATE [EP MONOGRAPH]

Common Name

English

PRAMIPEXOLE HYDROCHLORIDE HYDRATE

Common Name

English

OPRYMEA

Brand Name

English

Pramipexole dihydrochloride monohydrate [WHO-DD]

Common Name

English

PRAMIPEXOLE DIHYDROCHLORIDE [ORANGE BOOK]

Common Name

English

PRAMIPEXOLE HYDROCHLORIDE

Common Name

English

DAQUIRAN

Brand Name

English

PRAMIPEXOLE DIHYDROCHLORIDE MONOHYDRATE [MI]

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

PRAMIPEXOLE ACCORD (AUTHORIZED: RESTLESS LEGS SYNDROME)