DEXPRAMIPEXOLE

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 19 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 1064

Conditions

Condition	Modality	Targets	Highest Phase	Product
Amyotrophic lateral sclerosis 41 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25526593	Primary		Phase III 656	Unknown Approved Use Unknown
Stroke 144 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28320070	Primary		Not Provided 504	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 (total daily dose) 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 n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: https://pubmed.ncbi.nlm.nih.gov/22101764/	Other AEs: Upper respiratory tract infection, Anxiety... Other AEs: Upper respiratory tract infection (7%) Anxiety (11%) Muscular weakness (16%) Sinusitis (11%) Cough (11%) Constipation (25%) Insomnia (14%) Muscle spasticity (2%) Salivary hypersecretion (11%) Depression (11%) Dyspnea (14%) Dysarthria (11%) Dysphagia (9%) Fall (25%) Headache (14%) Dry mouth (16%) Oedema peripheral (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/22101764/

AEs

PubMed

Title	Date	PubMed
Increased risk of somnolence with the new dopamine agonists in patients with Parkinson's disease: a meta-analysis of randomised controlled trials.	2001	11665873
A study of excessive daytime sleepiness and its clinical significance in three groups of Parkinson's disease patients taking pramipexole, cabergoline and levodopa mono and combination therapy.	2001	11261748
Possible applications for dopaminergic agents following traumatic brain injury: part 2.	2001 Feb	11277855
Current advances in Parkinson's disease.	2001 Jul	11467283
[Use of dopamine agonists in the treatment of Parkinson's disease].	2002	12378886
Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression.	2002 Apr 3	11926889
[Pramipexole in Parkinson disease. Results of a treatment observation].	2002 Aug	12242961
Pramipexole for depression.	2002 Feb	11823287
Excessive daytime sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian Movement Disorders Group.	2002 Jan 23-30	11798367
Alopecia induced by dopamine agonists.	2002 Mar 12	11889256
A case of Parkinsonism due to lithium intoxication: treatment with Pramipexole.	2002 May	12093142
Gateways to Clinical Trials.	2002 Sep	12428432
Cabergoline, pramipexole and ropinirole used as monotherapy in early Parkinson's disease: an evidence-based comparison.	2003	12964891
Sleep attacks--facts and fiction: a critical review.	2003	12442691
Pramipexole increases vesicular dopamine uptake: implications for treatment of Parkinson's neurodegeneration.	2003 Aug 8	12921866
Fibromyalgia and pramipexole: promise and precaution.	2003 Dec	14719231
Pramipexole in Restless Legs syndrome. Evaluation by suggested immobilization test.	2003 Dec	14673586
Efficacy, safety, and tolerability of pramipexole in untreated and levodopa-treated patients with Parkinson's disease.	2003 Dec 15	14607306
Loss of color vision during long-term treatment with pramipexole.	2003 Jan	12528002
Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study.	2003 Jul	12823492
REAL and CALM: what have we learned?	2003 Jul	12815670
Randomized, double-blind, 3-month parallel study of the effects of pramipexole, pergolide, and placebo on Parkinsonian tremor.	2003 Nov	14639675
Pramipexole in the management of restless legs syndrome: an extended study.	2003 Nov 1	14655914
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
The effects of dopamine D3 agonists and antagonists in a nonhuman primate model of tardive dyskinesia.	2004 Aug	15301939
Quality of life in early Parkinson's disease: impact of dyskinesias and motor fluctuations.	2004 Jan	14743356
Predictors of impaired daytime sleep and wakefulness in patients with Parkinson disease treated with older (ergot) vs newer (nonergot) dopamine agonists.	2004 Jan	14732626
Slowing Parkinson's disease progression: recent dopamine agonist trials.	2004 Jan 27	14745094
Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.	2004 Jul	15262734
Pramipexole for bipolar II depression: a placebo-controlled proof of concept study.	2004 Jul 1	15219473
[Pharmacological profiles and clinical effects of antiparkinsonian agent, pramipexole].	2004 Jun	15170083
Conversion from dopamine agonists to pramipexole. An open-label trial in 227 patients with advanced Parkinson's disease.	2004 Mar	15015015
Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression.	2004 Mar	14992985
Furfuryl ethyl ether: important aging flavor and a new marker for the storage conditions of beer.	2004 Mar 24	15030227
Pramipexole for the treatment of uremic restless legs in patients undergoing hemodialysis.	2004 Mar 9	15007148
Restless legs symptoms in a patient with above knee amputations: a case of phantom restless legs.	2004 Mar-Apr	15252270
Pramipexole v. levodopa as initial treatment for Parkinson's disease: a randomized clinical-economic trial.	2004 Sep-Oct	15358996

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 `Sat Dec 16 17:56:03 UTC 2023` Edited by `admin` on `Sat Dec 16 17:56:03 UTC 2023`
Record UNII	WI638GUS96
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DEXPRAMIPEXOLE

Official 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

(R)-PRAMIPEXOLE

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