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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H28N4O.C4H4O4.H2O
Molecular Weight 474.55
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of TERGURIDE HYDROGEN MALEATE MONOHYDRATE

SMILES

O.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=FFZZPXNWIVRTAW-UWRDHRKBSA-N
InChI=1S/C20H28N4O.C4H4O4.H2O/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);1H2/b;2-1-;/t14-,16+,18+;;/m0../s1

HIDE SMILES / InChI

Description
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.

Originator

Sources: Collection of Czechoslovak Chemical Communications Volume 25, Pages 1922-8, Journal, 1960

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
25.0 nM [IC50]
4.0 nM [IC50]
69.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Teluron

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
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
Effects of several partial dopamine D2 receptor agonists in Cebus apella monkeys previously treated with haloperidol.
1993 Jun 24
Terguride attenuates prolactin levels and ameliorates insulin sensitivity and insulin binding in obese spontaneously hypertensive rats.
2001
Clinical features and medical treatment of male prolactinomas.
2001
A dopamine partial agonist and antagonist block amphetamine self-administration in a progressive ratio schedule.
2001 Apr
Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats.
2001 Aug
Dopamine partial agonist reverses amphetamine withdrawal in rats.
2001 Nov
Reinforcing effects of D2 dopamine receptor agonists and partial agonists in rhesus monkeys.
2001 Oct 1
[Results of treatment for male prolactinomas].
2002 Dec
Clustered ergot alkaloids modulate cell-mediated cytotoxicity.
2002 Feb
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
Terguride treatment attenuated prolactin release and enhanced insulin receptor affinity and GLUT 4 content in obese spontaneously hypertensive female, but not male rats.
2002 Jun
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.
2002 Nov
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
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
Effects of a partial dopamine D2-like agonist on the cocaine-induced behavioral sensitization of preweanling rats.
2003 Aug
Suppression of cocaine- and food-maintained behavior by the D2-like receptor partial agonist terguride in squirrel monkeys.
2003 Mar
Management of restless legs syndrome by the partial D2-agonist terguride.
2003 Sep
Pergolide, terguride and N,N'-spacer-linked oligomers of both interact with 5-HT2A receptors of rat tail artery.
2004
In vitro antiplasmodial activities of semisynthetic N,N'-spacer-linked oligomeric ergolines.
2004 Feb 15
Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats.
2005 Jan
Aripiprazole's low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic.
2005 May 16
Effects of terguride, ropinirole, and acetyl-L-carnitine on methamphetamine withdrawal in the rat.
2006 Mar
Recruitment of beta-arrestin2 to the dopamine D2 receptor: insights into anti-psychotic and anti-parkinsonian drug receptor signaling.
2008 Jun
Co-administration of the partial dopamine D2 agonist terguride with L-dopa attenuates L-dopa-induced locomotor sensitization in hemiparkinsonian mice.
2009 Sep 14
Increased expression of 5-hydroxytryptamine2A/B receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention.
2010 Nov
Patents

Sample Use Guides

Terguride was given orally in doses of 0.25 mg, 0.5 mg, and 1 mg.
Route of Administration: Oral
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.
Name Type Language
TERGURIDE HYDROGEN MALEATE MONOHYDRATE
Common Name English
TERGURIDE HYDROGEN MALEATE HYDRATE [MI]
Common Name English
UREA, N,N-DIETHYL-N'-((8.ALPHA.)-6-METHYLERGOLIN-8-YL)-, (2Z)-2-BUTENEDIOATE (1:1), MONOHYDRATE
Common Name English
Code System Code Type Description
FDA UNII
MVI7KL5PLQ
Created by admin on Sat Dec 16 11:01:12 GMT 2023 , Edited by admin on Sat Dec 16 11:01:12 GMT 2023
PRIMARY
MERCK INDEX
m10577
Created by admin on Sat Dec 16 11:01:12 GMT 2023 , Edited by admin on Sat Dec 16 11:01:12 GMT 2023
PRIMARY Merck Index
CAS
154592-36-6
Created by admin on Sat Dec 16 11:01:12 GMT 2023 , Edited by admin on Sat Dec 16 11:01:12 GMT 2023
PRIMARY
PUBCHEM
69445599
Created by admin on Sat Dec 16 11:01:12 GMT 2023 , Edited by admin on Sat Dec 16 11:01:12 GMT 2023
PRIMARY