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
SMILES
O.Cl.Cl.CCCN[C@@H]1CCC2=C(C1)SC(N)=N2
InChI
InChIKey=APVQOOKHDZVJEX-LSBIWMFESA-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-;;;/m1.../s1
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.
Approval Year
Cmax
| 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 |
T1/2
| 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
Other AEs: Upper respiratory tract infection, Anxiety... Other AEs: Upper respiratory tract infection (7%) Sources: 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%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Anxiety | 11% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Cough | 11% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Depression | 11% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Dysarthria | 11% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Salivary hypersecretion | 11% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Sinusitis | 11% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Dyspnea | 14% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Headache | 14% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Insomnia | 14% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Dry mouth | 16% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Muscular weakness | 16% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Muscle spasticity | 2% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Oedema peripheral | 2% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Constipation | 25% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Fall | 25% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Upper respiratory tract infection | 7% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
| Dysphagia | 9% | 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: |
unhealthy n = 44 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Sex: M+F Food Status: UNKNOWN Population Size: 44 Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| [Use of dopamine agonists in the treatment of Parkinson's disease]. | 2002 |
|
| [Pramipexole in Parkinson disease. Results of a treatment observation]. | 2002 Aug |
|
| Acute placebo-controlled sleep laboratory studies and clinical follow-up with pramipexole in restless legs syndrome. | 2002 Aug |
|
| [The usefulness of dopaminergic drugs in traumatic brain injury]. | 2002 Aug 16-31 |
|
| Pergolide-associated 'sleep attacks' in a patient with restless legs syndrome. | 2002 May |
|
| Do dopamine agonists or levodopa modify Parkinson's disease progression? | 2002 Nov |
|
| Neuroprotection in idiopathic Parkinson's disease. | 2002 Oct |
|
| Potential antidepressant properties of pramipexole detected in locomotor and operant behavioral investigations in mice. | 2002 Oct |
|
| Combination of two different dopamine agonists in the management of Parkinson's disease. | 2002 Sep |
|
| Gateways to Clinical Trials. | 2002 Sep |
|
| Pramipexole in routine clinical practice: a prospective observational trial in Parkinson's disease. | 2003 |
|
| Cabergoline, pramipexole and ropinirole used as monotherapy in early Parkinson's disease: an evidence-based comparison. | 2003 |
|
| Sleep attacks--facts and fiction: a critical review. | 2003 |
|
| Pathological gambling associated with dopamine agonist therapy in Parkinson's disease. | 2003 Aug 12 |
|
| Pramipexole inhibits MPTP toxicity in mice by dopamine D3 receptor dependent and independent mechanisms. | 2003 Aug 15 |
|
| Pramipexole increases vesicular dopamine uptake: implications for treatment of Parkinson's neurodegeneration. | 2003 Aug 8 |
|
| Pramipexole in Restless Legs syndrome. Evaluation by suggested immobilization test. | 2003 Dec |
|
| Efficacy, safety, and tolerability of pramipexole in untreated and levodopa-treated patients with Parkinson's disease. | 2003 Dec 15 |
|
| Loss of color vision during long-term treatment with pramipexole. | 2003 Jan |
|
| Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study. | 2003 Jul |
|
| REAL and CALM: what have we learned? | 2003 Jul |
|
| [Treatment of restless legs syndrome in uremic patients undergoing dialysis with pramipexole: preliminary results]. | 2003 Jun |
|
| The use of dopamine enhancing medications with children in low response states following brain injury. | 2003 Jun |
|
| [(123)I]beta-CIT SPECT is a useful method for monitoring dopaminergic degeneration in early stage Parkinson's disease. | 2003 Mar |
|
| The initial drug treatment of older patients with Parkinson's disease - consider an agonist, but don't demonise dopa. | 2003 May |
|
| Randomized, double-blind, 3-month parallel study of the effects of pramipexole, pergolide, and placebo on Parkinsonian tremor. | 2003 Nov |
|
| 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 Nov |
|
| Pramipexole in the management of restless legs syndrome: an extended study. | 2003 Nov 1 |
|
| The effects of pramipexole in REM sleep behavior disorder. | 2003 Nov 25 |
|
| Oral anticoagulation for ECG tremor artefact simulating atrial fibrillation. | 2003 Oct |
|
| Randomized, double-blind study of pramipexole with placebo and bromocriptine in advanced Parkinson's disease. | 2003 Oct |
|
| Treatment effects on nigrostriatal projection integrity in partial 6-OHDA lesions: comparison of L-DOPA and pramipexole. | 2003 Sep |
|
| Clinical strategies to prevent and delay motor complications. | 2003 Sep 23 |
|
| Low-dose pramipexole in the management of restless legs syndrome. An open label trial. | 2004 |
|
| [A comparative study of efficacy of dopamine receptors agonists and catechol-O-methyltransferase in the treatment of late stages of Parkinson's disease]. | 2004 |
|
| The effects of dopamine D3 agonists and antagonists in a nonhuman primate model of tardive dyskinesia. | 2004 Aug |
|
| Quality of life in early Parkinson's disease: impact of dyskinesias and motor fluctuations. | 2004 Jan |
|
| Predictors of impaired daytime sleep and wakefulness in patients with Parkinson disease treated with older (ergot) vs newer (nonergot) dopamine agonists. | 2004 Jan |
|
| Slowing Parkinson's disease progression: recent dopamine agonist trials. | 2004 Jan 27 |
|
| Slowing Parkinson's disease progression: recent dopamine agonist trials. | 2004 Jan 27 |
|
| Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. | 2004 Jul |
|
| Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. | 2004 Jul 1 |
|
| [Pharmacological profiles and clinical effects of antiparkinsonian agent, pramipexole]. | 2004 Jun |
|
| Conversion from dopamine agonists to pramipexole. An open-label trial in 227 patients with advanced Parkinson's disease. | 2004 Mar |
|
| Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. | 2004 Mar |
|
| Furfuryl ethyl ether: important aging flavor and a new marker for the storage conditions of beer. | 2004 Mar 24 |
|
| Pramipexole for the treatment of uremic restless legs in patients undergoing hemodialysis. | 2004 Mar 9 |
|
| Restless legs symptoms in a patient with above knee amputations: a case of phantom restless legs. | 2004 Mar-Apr |
|
| The activity of pramipexole in the mouse forced swim test is mediated by D2 rather than D3 receptors. | 2004 Sep |
|
| Pramipexole v. levodopa as initial treatment for Parkinson's disease: a randomized clinical-economic trial. | 2004 Sep-Oct |
Patents
Sample Use Guides
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).
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EU-Orphan Drug |
EU/3/09/616
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795J01AE70
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DTXSID10238291
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908244-04-2
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C167010
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100000174405
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WW-115
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46174453
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CHEMBL249420
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ACTIVE MOIETY
SUBSTANCE RECORD
