| 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
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
| Molecular Formula | C20H28N4O |
| Molecular Weight | 340.4625 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 3 / 3 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
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
Approval Year
Cmax
AUC
T1/2
Doses
AEs
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.
