DEXPRAMIPEXOLE

Investigational

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

Structure Search

SMILES

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

InChI

InChIKey=FASDKYOPVNHBLU-SSDOTTSWSA-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-/m1/s1

HIDE SMILES / InChI

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

Description
Sources: http://www.xconomy.com/boston/2013/01/03/biogen-idecs-als-drug-fails-phase-iii-trial/ | https://www.ncbi.nlm.nih.gov/pubmed/28320070 | https://www.ncbi.nlm.nih.gov/pubmed/25332381

Dexpramipexole (also known as KNS-760704/R-pramipexole) was originally developed by University of Virginia researchers to treat Amyotrophic Lateral Sclerosis and then was licensed to global biotechnology company Biogen Idec for further development. However, on phase III clinical trial the study of this drug was discontinued. Biogen said the drug neither slowed the loss of muscle function nor prolonged the lives of patients with ALS, often called Lou Gehrig’s disease. Nor did it show any efficacy in secondary endpoints of the clinical trial, or work in any sub-group of patients—about a big a failure as a company could have a Phase III trial. In addition, was discovered, that dexpramipexole was able to bind to beta-subunit of the mitochondrial F1/FO ATP synthase complex and increased its activity, thus reduced ischemic brain injury. These findings, together with the excellent brain penetration and favorable safety profile in humans, make dexpramipexole a drug with realistic translational potential for the treatment of stroke.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
ATP synthase subunit beta, mitochondrial 21 Target ID: P10719 Gene ID: 171374.0 Gene Symbol: Atp5b Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/28320070	Binding Agent 1076

Conditions

Condition	Modality	Targets	Highest Phase	Product
Amyotrophic lateral sclerosis 39 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25526593	Primary		Phase III 665	Unknown Approved Use Unknown
Stroke 144 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28320070	Primary		Not Provided 511	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
479 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20959524	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:		DEXPRAMIPEXOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
781 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20959524	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		DEXPRAMIPEXOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
3749 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20959524	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:		DEXPRAMIPEXOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8624 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20959524	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		DEXPRAMIPEXOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20959524	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:		DEXPRAMIPEXOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20959524	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		DEXPRAMIPEXOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
150 mg 2 times / day multiple, oral Highest studied dose Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22101764/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22101764/	Other AEs: Fall, Muscular weakness... Other AEs: Fall (25%) Muscular weakness (16%) Constipation (25%) Salivary hypersecretion (11%) Depression (11%) Dyspnea (14%) Dysarthria (11%) Dysphagia (9%) Headache (14%) Dry mouth (16%) Oedema peripheral (2%) Upper respiratory tract infection (7%) Anxiety (11%) Sinusitis (11%) Cough (11%) Insomnia (14%) Muscle spasticity (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/22101764/

AEs

PubMed

Title	Date	PubMed
Pramipexole v. levodopa as initial treatment for Parkinson's disease: a randomized clinical-economic trial.	2004-09-11	15358996
The activity of pramipexole in the mouse forced swim test is mediated by D2 rather than D3 receptors.	2004-09	14985923
The effects of dopamine D3 agonists and antagonists in a nonhuman primate model of tardive dyskinesia.	2004-08	15301939
Restless legs symptoms in a patient with above knee amputations: a case of phantom restless legs.	2004-07-15	15252270
Pramipexole for bipolar II depression: a placebo-controlled proof of concept study.	2004-07-01	15219473
Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.	2004-07	15262734
[Pharmacological profiles and clinical effects of antiparkinsonian agent, pramipexole].	2004-06	15170083
Furfuryl ethyl ether: important aging flavor and a new marker for the storage conditions of beer.	2004-03-24	15030227
Pramipexole for the treatment of uremic restless legs in patients undergoing hemodialysis.	2004-03-09	15007148
Conversion from dopamine agonists to pramipexole. An open-label trial in 227 patients with advanced Parkinson's disease.	2004-03	15015015
Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression.	2004-03	14992985
Slowing Parkinson's disease progression: recent dopamine agonist trials.	2004-01-27	14750218
Slowing Parkinson's disease progression: recent dopamine agonist trials.	2004-01-27	14745094
Quality of life in early Parkinson's disease: impact of dyskinesias and motor fluctuations.	2004-01	14743356
Predictors of impaired daytime sleep and wakefulness in patients with Parkinson disease treated with older (ergot) vs newer (nonergot) dopamine agonists.	2004-01	14732626
Augmentation and tolerance with long-term pramipexole treatment of restless legs syndrome (RLS).	2004-01	14725821
Low-dose pramipexole in the management of restless legs syndrome. An open label trial.	2004	15179023
[A comparative study of efficacy of dopamine receptors agonists and catechol-O-methyltransferase in the treatment of late stages of Parkinson's disease].	2004	14870689
Efficacy, safety, and tolerability of pramipexole in untreated and levodopa-treated patients with Parkinson's disease.	2003-12-15	14607306
Fibromyalgia and pramipexole: promise and precaution.	2003-12	14719231
Pramipexole in Restless Legs syndrome. Evaluation by suggested immobilization test.	2003-12	14673586
The effects of pramipexole in REM sleep behavior disorder.	2003-11-25	14638967
Pramipexole in the management of restless legs syndrome: an extended study.	2003-11-01	14655914
Randomized, double-blind, 3-month parallel study of the effects of pramipexole, pergolide, and placebo on Parkinsonian tremor.	2003-11	14639675
Neuroprotective effects of the novel D3/D2 receptor agonist and antiparkinson agent, S32504, in vitro against 1-methyl-4-phenylpyridinium (MPP+) and in vivo against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a comparison to ropinirole.	2003-11	14637109
Oral anticoagulation for ECG tremor artefact simulating atrial fibrillation.	2003-10	14609309
Randomized, double-blind study of pramipexole with placebo and bromocriptine in advanced Parkinson's disease.	2003-10	14534919
Clinical strategies to prevent and delay motor complications.	2003-09-23	14504375
Treatment effects on nigrostriatal projection integrity in partial 6-OHDA lesions: comparison of L-DOPA and pramipexole.	2003-09	12957491
Pramipexole inhibits MPTP toxicity in mice by dopamine D3 receptor dependent and independent mechanisms.	2003-08-15	12954356
Pathological gambling associated with dopamine agonist therapy in Parkinson's disease.	2003-08-12	12913220
Pramipexole increases vesicular dopamine uptake: implications for treatment of Parkinson's neurodegeneration.	2003-08-08	12921866
Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study.	2003-07	12823492
REAL and CALM: what have we learned?	2003-07	12815670
Reduction of oxidative stress in amyotrophic lateral sclerosis following pramipexole treatment.	2003-06	14506939
[Treatment of restless legs syndrome in uremic patients undergoing dialysis with pramipexole: preliminary results].	2003-06	12942600
The use of dopamine enhancing medications with children in low response states following brain injury.	2003-06	12745705
The initial drug treatment of older patients with Parkinson's disease - consider an agonist, but don't demonise dopa.	2003-05	12720606
Pramipexole in Parkinson's disease. A short-term study using the combined levodopa-dopamine agonist test.	2003-04-05	12675263
Pramipexole in comparison to l-dopa: a neuropsychological study.	2003-04	12658365
[(123)I]beta-CIT SPECT is a useful method for monitoring dopaminergic degeneration in early stage Parkinson's disease.	2003-03	12588911
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.	2003-02	12539211
Multiple blood donations associated with iron deficiency in patients with restless legs syndrome.	2003-01	12528877
Loss of color vision during long-term treatment with pramipexole.	2003-01	12528002
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
Neuroprotection in idiopathic Parkinson's disease.	2002-10	12522567
Combination of two different dopamine agonists in the management of Parkinson's disease.	2002-09	12548370
Pergolide-associated 'sleep attacks' in a patient with restless legs syndrome.	2002-05	14592219

Patents

Sample Use Guides

In Vivo Use Guide

Oral tablet 150 mg twice daily for up to 18 months

Route of Administration: Oral

In Vitro Use Guide

It was found that dexpramipexole (DEX) binds to the oligomycin sensitivity–conferring protein (OSCP) and b-subunits of the F1/FO ATP synthase, suggesting that it may indirectly inhibit the c-subunit (mPTP) pore by producing a conformational change in complex V that places F1 over the pore, inhibiting its conductance. The human open reading frame constructs for α, β, b, c, δ, d, ε, γ, and oligomycin sensitivity–conferring protein (OSCP) ATP synthase subunits were used. 293T cells were transfected with the above constructs. On day 3 post-transfection, the cells were lysed. The proteins were eluted from a portion of the samples, and the presence of the proteins on the beads was verified by immunoblot analysis, using mouse anti-Myc antibodies. The protein-bound beads were incubated in the presence of [14C]DEX (range of concentration was: 1-10 uM).

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:48:16 GMT 2025` Edited by `admin` on `Wed Apr 02 09:48:16 GMT 2025`
Record UNII	WI638GUS96
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DEXPRAMIPEXOLE

Official Name

English

(R)-PRAMIPEXOLE

Preferred Name

English

R-(+)-PRAMIPEXOLE

Common Name

English

2,6-BENZOTHIAZOLEDIAMINE, 4,5,6,7-TETRAHYDRO-N6-PROPYL-, (R)-

Systematic Name

English

DEXPRAMIPEXOLE [USAN]

Common Name

English

(6R)-N6-PROPYL-4,5,6,7-TETRAHYDRO-1,3-BENZOTHIAZOLE-2,6-DIAMINE

Systematic Name

English

2,6-BENZOTHIAZOLEDIAMINE, 4,5,6,7-TETRAHYDRO-N6-PROPYL-, (6R)-

Systematic Name

English

dexpramipexole [INN]

Common Name

English

Dexpramipexole [WHO-DD]

Common Name

English

(R)-4,5,6,7-TETRAHYDRO-6-(PROPYLAMINO)-BENZOTHIAZOLE-2-AMINE

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

681319