Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C20H28N4O.C4H4O4 |
Molecular Weight | 456.5347 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C/C(O)=O.[H][C@@]12CC3=CNC4=CC=CC(=C34)[C@@]1([H])C[C@@H](CN2C)NC(=O)N(CC)CC
InChI
InChIKey=SORAZNWVQFKAFD-IBIFCFAISA-N
InChI=1S/C20H28N4O.C4H4O4/c1-4-24(5-2)20(25)22-14-10-16-15-7-6-8-17-19(15)13(11-21-17)9-18(16)23(3)12-14;5-3(6)1-2-4(7)8/h6-8,11,14,16,18,21H,4-5,9-10,12H2,1-3H3,(H,22,25);1-2H,(H,5,6)(H,7,8)/b;2-1-/t14-,16+,18+;/m0./s1
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/22049464Curator's Comment: description was created based on several sources, including
https://www.drugs.com/international/terguride.html | https://www.ncbi.nlm.nih.gov/pubmed/2571729 | https://www.ncbi.nlm.nih.gov/pubmed/11520375 | https://www.ncbi.nlm.nih.gov/pubmed/3127243
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22049464
Curator's Comment: description was created based on several sources, including
https://www.drugs.com/international/terguride.html | https://www.ncbi.nlm.nih.gov/pubmed/2571729 | https://www.ncbi.nlm.nih.gov/pubmed/11520375 | https://www.ncbi.nlm.nih.gov/pubmed/3127243
Terguride (INN), also known as trans-dihydrolisuride, is a serotonin receptor antagonist and dopamine receptor agonist of the ergoline family. Terguride is approved for and used in the treatment of hyperprolactinemia. Terguride is an oral, potent antagonist of 5-HT2B and 5-HT2A (serotonin) receptors. Serotonin stimulates the proliferation of pulmonary artery smooth muscle cells and induces fibrosis in the wall of pulmonary arteries. Together, this causes vascular remodeling and narrowing of the pulmonary arteries. These changes result in increased vascular resistance and PAH. Due to the potential anti-proliferative and anti-fibrotic activity of terguride, this potential medicine could offer the hope of achieving reversal of pulmonary artery vascular remodeling and attenuation of disease progression. In May 2008, terguride was granted orphan drug status for the treatment of pulmonary arterial hypertension. In May 2010 Pfizer purchased worldwide rights for the drug.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL273 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2571729 |
25.0 nM [IC50] | ||
Target ID: CHEMBL339 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2571729 |
4.0 nM [IC50] | ||
Target ID: CHEMBL265 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2571729 |
69.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Teluron Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Transdihydrolisuride in parkinsonism. | 1987 |
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Behavioural profile of partial D2 dopamine receptor agonists. 1. Atypical inhibition of d-amphetamine-induced locomotor hyperactivity and stereotypy. | 1991 |
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Antagonist effect of terguride in Parkinson's disease. | 1991 Oct |
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Effect of D1 and D2 agonists and antagonists on dyskinesia produced by L-dopa in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys. | 1991 Oct |
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Effects of terguride, a partial D2 agonist, on MPTP-lesioned parkinsonian cynomolgus monkeys. | 1993 May |
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Effects of terguride on anterior pituitary function in parkinsonian patients treated with L-dopa: a double-blind study versus placebo. | 1996 Feb |
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A dopamine partial agonist and antagonist block amphetamine self-administration in a progressive ratio schedule. | 2001 Apr |
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Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats. | 2001 Aug |
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Dopamine partial agonist reverses amphetamine withdrawal in rats. | 2001 Nov |
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Reinforcing effects of D2 dopamine receptor agonists and partial agonists in rhesus monkeys. | 2001 Oct 1 |
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Atypical kinetics for a series of putative dopamine antagonists to reverse the low-magnitude Ca2+ phase in the dopamine-bound D2short receptor state. | 2002 Jan |
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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 |
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[Pharmacokinetic/pharmacodynamic analysis of anti-hyperprolactinemic effect of terguride based on dopamine D2 receptor occupancy]. | 2003 Apr |
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Suppression of cocaine- and food-maintained behavior by the D2-like receptor partial agonist terguride in squirrel monkeys. | 2003 Mar |
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Effects of terguride treatment on glucose abnormalities induced by ischemic brain damage in SHR/N-cp lean Koletsky strain and in rats of Wistar strain. | 2004 |
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In vitro antiplasmodial activities of semisynthetic N,N'-spacer-linked oligomeric ergolines. | 2004 Feb 15 |
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Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats. | 2005 Jan |
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Aripiprazole's low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic. | 2005 May 16 |
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Effects of a partial D2-like receptor agonist on striatal dopamine autoreceptor functioning in preweanling rats. | 2006 Feb 16 |
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Effects of terguride, ropinirole, and acetyl-L-carnitine on methamphetamine withdrawal in the rat. | 2006 Mar |
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[A case of ruptured internal carotid artery aneurysm mimicking pituitary apoplexy]. | 2007 Dec |
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Effects of aripiprazole and terguride on dopamine synthesis in the dorsal striatum and medial prefrontal cortex of preweanling rats. | 2008 |
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Recognition properties and competitive assays of a dual dopamine/serotonin selective molecularly imprinted polymer. | 2008 Dec |
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Recruitment of beta-arrestin2 to the dopamine D2 receptor: insights into anti-psychotic and anti-parkinsonian drug receptor signaling. | 2008 Jun |
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Development and application of an LC-MS/MS method for measuring the effect of (partial) agonists on cAMP accumulation in vitro. | 2010 Apr 30 |
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The dopamine D(2) partial agonist and antagonist terguride decreases heroin self-administration on fixed- and progressive-ratio schedules. | 2010 Dec |
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Evaluation of the efficacy and safety of terguride in patients with fibromyalgia syndrome: results of a twelve-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. | 2010 Jan |
|
Increased expression of 5-hydroxytryptamine2A/B receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention. | 2010 Nov |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3127243
Terguride was given orally in doses of 0.25 mg, 0.5 mg, and 1 mg.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22049464
Collagen synthesis activity was assessed by measuring the incorporation of [3H]proline as follows: 3 x 104 cells were seeded in 24-well plates and grown overnight in DMEM/F12 medium supplemented with 10% dialyzed fetal calf serum and penicillin/streptomycin. The medium was replaced with a low serum concentration of 0.5%. After 48 h the cells were incubated in DMEM/F12 supplemented with 10 mkM phenelzine (a nonselective monoamine oxidase inhibitor) and 0.6 mM ascorbic acid. 5-HT (in the absence and presence of terguride) and terguride alone were added. Terguride was added 30 min before 5-HT. Cells were then incubated for 48 h in the presence of 1 mkCi/ml [3H]proline. Cells were washed twice with ice-cold PBS before precipitation with ice-cold 10% trichloroacetic acid for 1 h at 4°C. The precipitates were solubilized in 0.3 N NaOH/0.1% SDS solution at 37°C under gentle agitation, mixed with scintillation cocktail, and measured in a beta-scintillation counter. Experiments were performed in triplicate or quadruplicate. Results are presented as fold-changes compared with untreated control cells.
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37686-85-4
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m10577
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20839521
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253-625-8
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SUB04725MIG
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100000084813
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U5WJP6R7AH
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ACTIVE MOIETY
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