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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H28N4O
Molecular Weight 340.4625
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TERGURIDE

SMILES

[H][C@@]12CC3=CNC4=CC=CC(=C34)[C@@]1([H])C[C@@H](CN2C)NC(=O)N(CC)CC

InChI

InChIKey=JOAHPSVPXZTVEP-YXJHDRRASA-N
InChI=1S/C20H28N4O/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/h6-8,11,14,16,18,21H,4-5,9-10,12H2,1-3H3,(H,22,25)/t14-,16+,18+/m0/s1

HIDE SMILES / InChI

Molecular Formula C20H28N4O
Molecular Weight 340.4625
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

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
Antagonist effect of terguride in Parkinson's disease.
1991 Oct
Partial dopamine agonist therapy of levodopa-induced dyskinesias.
1992 Jun
Effects of several partial dopamine D2 receptor agonists in Cebus apella monkeys previously treated with haloperidol.
1993 Jun 24
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
Clinical features and medical treatment of male prolactinomas.
2001
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
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. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.
2002 Nov
[Pharmacokinetic/pharmacodynamic analysis of anti-hyperprolactinemic effect of terguride based on dopamine D2 receptor occupancy].
2003 Apr
Effects of a partial dopamine D2-like agonist on the cocaine-induced behavioral sensitization of preweanling rats.
2003 Aug
[Arrest of lactation after 2nd trimester abortion with a single dose of cabergoline in comparison with 10-day administration of teguride].
2003 Jan
Suppression of cocaine- and food-maintained behavior by the D2-like receptor partial agonist terguride in squirrel monkeys.
2003 Mar
Pergolide, terguride and N,N'-spacer-linked oligomers of both interact with 5-HT2A receptors of rat tail artery.
2004
In vitro characterization of SLV308 (7-[4-methyl-1-piperazinyl]-2(3H)-benzoxazolone, monohydrochloride): a novel partial dopamine D2 and D3 receptor agonist and serotonin 5-HT1A receptor agonist.
2006 Dec 15
Pre- and postsynaptic actions of a partial D2 receptor agonist in reserpinized young rats: longevity of agonistic effects.
2006 Dec 8
Effects of terguride, ropinirole, and acetyl-L-carnitine on methamphetamine withdrawal in the rat.
2006 Mar
The partial dopamine D2-like receptor agonist terguride functions as an agonist in preweanling rats after a 5-day reserpine regimen.
2006 Mar
[A case of ruptured internal carotid artery aneurysm mimicking pituitary apoplexy].
2007 Dec
Long-term serotonin effects in the rat are prevented by terguride.
2007 Oct 4
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
Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes.
2008 Jan
Recruitment of beta-arrestin2 to the dopamine D2 receptor: insights into anti-psychotic and anti-parkinsonian drug receptor signaling.
2008 Jun
The effect of terguride in carbon tetrachloride-induced liver fibrosis in rat.
2008 Nov
Dopamine receptor subtypes contribution to Homer1a induction: insights into antipsychotic molecular action.
2009 Aug 1
Co-administration of the partial dopamine D2 agonist terguride with L-dopa attenuates L-dopa-induced locomotor sensitization in hemiparkinsonian mice.
2009 Sep 14
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:58:45 GMT 2023
Edited
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on Fri Dec 15 15:58:45 GMT 2023
Record UNII
21OJT43Q88
Record Status Validated (UNII)
Record Version
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Name Type Language
TERGURIDE
INN   JAN   MART.   MI   WHO-DD  
INN  
Official Name English
Terguride [WHO-DD]
Common Name English
terguride [INN]
Common Name English
1,1-DIETHYL-3-(6-METHYLERGOLIN-8.ALPHA.-YL)UREA
Systematic Name English
TELURON
Brand Name English
TERGURIDE [MART.]
Common Name English
TERGURIDE [MI]
Common Name English
TERGURIDE [JAN]
Common Name English
Classification Tree Code System Code
WHO-ATC G02CB06
Created by admin on Fri Dec 15 15:58:45 GMT 2023 , Edited by admin on Fri Dec 15 15:58:45 GMT 2023
FDA ORPHAN DRUG 380512
Created by admin on Fri Dec 15 15:58:45 GMT 2023 , Edited by admin on Fri Dec 15 15:58:45 GMT 2023
FDA ORPHAN DRUG 255007
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NCI_THESAURUS C47794
Created by admin on Fri Dec 15 15:58:45 GMT 2023 , Edited by admin on Fri Dec 15 15:58:45 GMT 2023
EU-Orphan Drug EU/3/13/1104
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WHO-VATC QG02CB06
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NCI_THESAURUS C66884
Created by admin on Fri Dec 15 15:58:45 GMT 2023 , Edited by admin on Fri Dec 15 15:58:45 GMT 2023
Code System Code Type Description
SMS_ID
100000091952
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PRIMARY
DRUG CENTRAL
2601
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PRIMARY
IUPHAR
56
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PRIMARY
ECHA (EC/EINECS)
253-624-2
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PRIMARY
INN
5437
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PRIMARY
WIKIPEDIA
Terguride
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PRIMARY
EVMPD
SUB10923MIG
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PRIMARY
ChEMBL
CHEMBL73151
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PRIMARY
MESH
C006208
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PRIMARY
CAS
37686-84-3
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PRIMARY
PUBCHEM
443951
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PRIMARY
MERCK INDEX
m10577
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PRIMARY Merck Index
DRUG BANK
DB13399
Created by admin on Fri Dec 15 15:58:45 GMT 2023 , Edited by admin on Fri Dec 15 15:58:45 GMT 2023
PRIMARY
NCI_THESAURUS
C152567
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PRIMARY
EPA CompTox
DTXSID3045809
Created by admin on Fri Dec 15 15:58:45 GMT 2023 , Edited by admin on Fri Dec 15 15:58:45 GMT 2023
PRIMARY
FDA UNII
21OJT43Q88
Created by admin on Fri Dec 15 15:58:45 GMT 2023 , Edited by admin on Fri Dec 15 15:58:45 GMT 2023
PRIMARY
Related Record Type Details
TARGET->PARTIAL AGONIST
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TARGET->PARTIAL AGONIST
Emax = 90%
EC50
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ACTIVE MOIETY