U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

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
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
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
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. 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
Agonism at 5-HT2B receptors is not a class effect of the ergolines.
2005 Apr 25
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
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
Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes.
2008 Jan
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 Sat Dec 16 18:48:14 GMT 2023
Edited
by admin
on Sat Dec 16 18:48:14 GMT 2023
Record UNII
U5WJP6R7AH
Record Status Validated (UNII)
Record Version
  • Download
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
Related Record Type Details
SOLVATE->ANHYDROUS
Related Record Type Details
ACTIVE MOIETY