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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
Structure of TERGURIDE HYDROGEN MALEATE

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

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
Transdihydrolisuride in parkinsonism.
1987
Behavioural profile of partial D2 dopamine receptor agonists. 1. Atypical inhibition of d-amphetamine-induced locomotor hyperactivity and stereotypy.
1991
Antagonist effect of terguride in Parkinson's disease.
1991 Oct
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 terguride, a partial D2 agonist, on MPTP-lesioned parkinsonian cynomolgus monkeys.
1993 May
Effects of terguride on anterior pituitary function in parkinsonian patients treated with L-dopa: a double-blind study versus placebo.
1996 Feb
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
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
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
[Pharmacokinetic/pharmacodynamic analysis of anti-hyperprolactinemic effect of terguride based on dopamine D2 receptor occupancy].
2003 Apr
Suppression of cocaine- and food-maintained behavior by the D2-like receptor partial agonist terguride in squirrel monkeys.
2003 Mar
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
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 a partial D2-like receptor agonist on striatal dopamine autoreceptor functioning in preweanling rats.
2006 Feb 16
Effects of terguride, ropinirole, and acetyl-L-carnitine on methamphetamine withdrawal in the rat.
2006 Mar
[A case of ruptured internal carotid artery aneurysm mimicking pituitary apoplexy].
2007 Dec
Effects of aripiprazole and terguride on dopamine synthesis in the dorsal striatum and medial prefrontal cortex of preweanling rats.
2008
Recognition properties and competitive assays of a dual dopamine/serotonin selective molecularly imprinted polymer.
2008 Dec
Recruitment of beta-arrestin2 to the dopamine D2 receptor: insights into anti-psychotic and anti-parkinsonian drug receptor signaling.
2008 Jun
Development and application of an LC-MS/MS method for measuring the effect of (partial) agonists on cAMP accumulation in vitro.
2010 Apr 30
The dopamine D(2) partial agonist and antagonist terguride decreases heroin self-administration on fixed- and progressive-ratio schedules.
2010 Dec
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
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
MI  
Common Name English
SH-406
Code English
VUFB-6638
Code English
MYSALFON
Brand Name English
TERGURIDE HYDROGEN MALEATE [MI]
Common Name English
N,N-DIETHYL-N'-(D-6-METHYL-10.ALPHA.-ISOERGOLIN-8-YL)UREA HYDROGEN MALEATE
Common Name English
DIRONYL
Brand Name English
TERGURIDE HYDROGENMALEATE
WHO-DD  
Common Name English
ZK-31224
Code English
UREA, N,N-DIETHYL-N'-((8.ALPHA.)-6-METHYLERGOLIN-8-YL)-, (2Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
Terguride hydrogenmaleate [WHO-DD]
Common Name English
Code System Code Type Description
CAS
37686-85-4
Created by admin on Sat Dec 16 18:48:14 GMT 2023 , Edited by admin on Sat Dec 16 18:48:14 GMT 2023
PRIMARY
MERCK INDEX
m10577
Created by admin on Sat Dec 16 18:48:14 GMT 2023 , Edited by admin on Sat Dec 16 18:48:14 GMT 2023
PRIMARY Merck Index
PUBCHEM
20839521
Created by admin on Sat Dec 16 18:48:14 GMT 2023 , Edited by admin on Sat Dec 16 18:48:14 GMT 2023
PRIMARY
ECHA (EC/EINECS)
253-625-8
Created by admin on Sat Dec 16 18:48:14 GMT 2023 , Edited by admin on Sat Dec 16 18:48:14 GMT 2023
PRIMARY
EVMPD
SUB04725MIG
Created by admin on Sat Dec 16 18:48:14 GMT 2023 , Edited by admin on Sat Dec 16 18:48:14 GMT 2023
PRIMARY
SMS_ID
100000084813
Created by admin on Sat Dec 16 18:48:14 GMT 2023 , Edited by admin on Sat Dec 16 18:48:14 GMT 2023
PRIMARY
FDA UNII
U5WJP6R7AH
Created by admin on Sat Dec 16 18:48:14 GMT 2023 , Edited by admin on Sat Dec 16 18:48:14 GMT 2023
PRIMARY