TALIPEXOLE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H15N3S
Molecular Weight	209.311
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC2=C(CCN(CC=C)CC2)S1

InChI

InChIKey=DHSSDEDRBUKTQY-UHFFFAOYSA-N

InChI=1S/C10H15N3S/c1-2-5-13-6-3-8-9(4-7-13)14-10(11)12-8/h2H,1,3-7H2,(H2,11,12)

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Description
Sources: http://link.springer.com/article/10.2165/00023210-199707050-00007
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/8842679

Talipexole is a D2 receptor agonist which was marketed in June 1996 in Japan for the treatment of Parkinson's disease. Clinical trials with talipexole in patients with Parkinson's disease demonstrated statistically significant improvements from baseline for parkinsonian symptoms including akinesia, rigidity, tremor and gait disturbances.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: http://www.ncbi.nlm.nih.gov/pubmed/10455328	Agonist 2678	5.8 null [pKi]
Dopamine D3 receptor 91 Target ID: CHEMBL234 Sources: http://www.ncbi.nlm.nih.gov/pubmed/10455328	Agonist 2678	7.0 null [pKi]
Alpha-2a adrenergic receptor 63 Target ID: CHEMBL1867 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12388666	Agonist 2678	7.43 null [pKi]
Alpha-2b adrenergic receptor 27 Target ID: CHEMBL1942 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12388666	Agonist 2678	7.09 null [pKi]
Alpha-2c adrenergic receptor 37 Target ID: CHEMBL1916 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12388666	Agonist 2678	7.37 null [pKi]
Dopamine D4 receptor 71 Target ID: CHEMBL219 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12388666	Agonist 2678	6.48 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic schizophrenia 6 Sources: http://www.ncbi.nlm.nih.gov/pubmed/8102551	Primary		Preclinical	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: http://link.springer.com/article/10.2165/00023210-199707050-00007	Primary		Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Release and aggregation of cytochrome c and alpha-synuclein are inhibited by the antiparkinsonian drugs, talipexole and pramipexole.	2001 Apr 6	11301060
Identification of the dopamine autoreceptor in the guinea-pig retina as D(2) receptor using novel subtype-selective antagonists.	2001 Aug	11498509
Postjunctional alpha(2C)-adrenoceptor contractility in human saphenous vein.	2001 Feb 16	11226402
Receptor reserve analysis of the human alpha(2C)-adrenoceptor using.	2001 Jan 12	11164378
Nonlinear analysis of partial dopamine agonist effects on cAMP in C6 glioma cells.	2001 Jan-Feb	11489662
[A-56-year-old woman with parkinsonism, whose mother had Parkinson's disease].	2001 May	11428377
Analysis of ligand activation of alpha 2-adrenoceptor subtypes under conditions of equal G alpha protein stoichiometry.	2001 May	11383713
Modulation of ligand responses by coupling of alpha(2A)-adrenoceptors to diverse G(alpha)-proteins.	2001 May 1	11301041
Intranasal application of the alpha2-adrenoceptor agonist BHT-920 produces decongestion in the cat.	2001 Nov-Dec	11777250
alpha(2)-adrenoceptor antagonist properties of OPC-28326, a novel selective peripheral vasodilator.	2001 Oct	11606316
Alpha2-adrenoceptor ligands inhibit alpha1-adrenoceptor-mediated contraction of isolated rat arteries.	2002 Aug	12570016
Influence of sildenafil on central dopamine-mediated behaviour in male rats.	2002 Feb 15	11895101
Neuroleptic-like profile of the cannabinoid agonist, HU 210, on rodent behavioural models.	2002 Jan	11853125
Impaired endothelial alpha-2 adrenergic receptor-mediated vascular relaxation in the fructose-fed rat.	2002 Mar	12047035
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor.	2002 Nov	12388667
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
Inhibitory effects of D2 agonists by striatal injection on excessive release of dopamine and hyperactivity induced by Bay K 8644 in rats.	2003	12732253
Piribedil enhances frontocortical and hippocampal release of acetylcholine in freely moving rats by blockade of alpha 2A-adrenoceptors: a dialysis comparison to talipexole and quinelorane in the absence of acetylcholinesterase inhibitors.	2003 Apr	12649387
Paraquat leads to dopaminergic neural vulnerability in organotypic midbrain culture.	2003 Aug	12871774
Repeated administration of methamphetamine causes hypersensitivity of D2 receptor in rat ventral tegmental area.	2003 Aug 21	12873735
Prolonged drug-induced hypothermia in experimental stroke.	2003 Mar-Apr	17903912
Effects of an alpha2-adrenoceptor agonist in nasal mucosa.	2003 Oct	15764068
Blood pressure and alpha-vascular reactivity in hypertensive rats treated with amlodipine and dietary Ca.	2004 Apr 5	15063161
Immunohistochemical and functional evidence for a noradrenergic regulation in the horse penile deep dorsal vein.	2004 Dec	15057259
An update on the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder.	2004 May 1	15164915
Practice parameters for the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder.	2004 May 1	15164914
Low dose pramipexole is neuroprotective in the MPTP mouse model of Parkinson's disease, and downregulates the dopamine transporter via the D3 receptor.	2004 Oct 11	15473914
Drug treatment of Parkinson's disease.	2004 Sep	22033779
Antagonistic activity of ascorbic acid (vitamin C) on dopaminergic modulation: apomorphine-induced stereotypic behavior in mice.	2006	16569938
Pre-junctional alpha2-adrenoceptors modulation of the nitrergic transmission in the pig urinary bladder neck.	2007	17266136
alpha2-adrenoceptor agonists as nasal decongestants.	2007	16809058
MPP(+)-induced cytotoxicity in neuroblastoma cells: Antagonism and reversal by guanosine.	2007 Sep	18404453
Pharmacological modulation of dopaminergic brain activity and its reflection in spectral frequencies of the rat electropharmacogram.	2008	19142029
Mechanism of decongestant activity of alpha 2-adrenoceptor agonists.	2008	17869148
Clinical characteristics of restless legs syndrome in end-stage renal failure and idiopathic RLS patients.	2008 Apr 30	18074382
Dopamine receptor agonists reverse behavioral abnormalities of alpha-synuclein transgenic mouse, a new model of Parkinson's disease.	2008 Feb 15	17896793
Genetic findings in Parkinson's disease and translation into treatment: a leading role for mitochondria?	2008 Mar	17680806
The frequency of cardiac valvular regurgitation in Parkinson's disease.	2008 May 15	18398916
Bromocriptine, a dopamine D(2) receptor agonist with the structure of the amino acid ergot alkaloids, induces neurite outgrowth in PC12 cells.	2008 Nov 19	18835264
Effective control of catatonia in Parkinson's disease by electroconvulsive therapy: a case report.	2009 Feb	19146631
Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free radicals and reduces cell injury.	2009 Jan-Mar	20046643
Pharmacokinetic profile of talipexole in healthy volunteers is not altered when it is co-administered with Madopar (co-beneldopa).	2009 Jun	19646081
Oxidative neurodegeneration is prevented by UCP0045037, an allosteric modulator for the reduced form of DJ-1, a wild-type of familial Parkinson's disease-linked PARK7.	2009 Nov 5	20087465
The neuroprotective effect of talipexole from paraquat-induced cell death in dopaminergic neuronal cells.	2010 Dec	20673835
Effect of bromocriptine on the severity of ovarian hyperstimulation syndrome and outcome in high responders undergoing assisted reproduction.	2010 May	21209752
[Dopaminergic neuroprotection and reconstruction of neural network tiara].	2010 Oct	20930477

Patents

Sample Use Guides

In Vivo Use Guide

Initially 0.2 or 0-4 mg/day, increased by 0.4 mg every week (usual maintenance dosage 1.2 to 3.6 mg/day) Below 0.8 mg/day, once a day; 0.8 to 1.2 mg/day, twice a day; over 1.2 mg/day, 3 times a day

Route of Administration: Oral

In Vitro Use Guide

Talipexole at low concentration (0.1-1 mM) significantly inhibited the accumulation of cytochrome c in the cytosolic fraction of human neuroblastoma SH-SY5Y cells

Name

Type

Language

TALIPEXOLE

Official Name

English

6-ALLYL-2-AMINO-5,6,7,8-TETRAHYDRO-4H-THIAZOLO(4,5-D)AZEPINE

Systematic Name

English

talipexole [INN]

Common Name

English

Talipexole [WHO-DD]

Common Name

English

TALIPEXOLE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66884