Terguride

Last updated
Terguride
Terguride.png
Clinical data
Trade names Teluron
Other namesDironyl; Mysalfon; trans-Dihydrolisuride; Transdihydrolisuride; TDHL; SH-406; VUFB-6638; ZK-31224; N,N-Diethyl-N'-[(8α)-6-methylergolin-8-yl]urea
AHFS/Drugs.com International Drug Names
Routes of
administration 		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
  • 3-[(6aR,9S,10aR)-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard 100.048.732 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C20H28N4O
Molar mass 340.471 g·mol−1
3D model (JSmol)
  • CCN(CC)C(=O)N[C@H]1C[C@H]2[C@@H](CC3=CNC4=CC=CC2=C34)N(C1)C
  • 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
  • Key:JOAHPSVPXZTVEP-YXJHDRRASA-N
   (verify)

Terguride (INN Tooltip International Nonproprietary Name, JAN Tooltip Japanese Accepted Name), sold under the brand name Teluron, is a serotonin receptor antagonist and dopamine receptor agonist of the ergoline family. It is approved for and used as a prolactin inhibitor in the treatment of hyperprolactinemia (high prolactin levels) in Japan. [1] [2] Terguride is taken by mouth.[ citation needed ]

Contents

Pharmacology

Pharmacodynamics

Terguride acts as an agonist of the dopamine D2 receptor and as an antagonist of the serotonin 5-HT2A and 5-HT2B receptors, among other actions.[ citation needed ]

As an antagonist of the 5-HT2B receptor, terguride is not associated with cardiac valvulopathy. [3]

Activities of terguride at various sites [4] [5] [6] [7]
SiteAffinity (Ki [nM])Efficacy (Emax [%])Action
D1 28 ? ?
D2S 0.8139Partial agonist
D2L 1.10Silent antagonist
D3 1.036Partial agonist
D4 8.10Silent antagonist
D5 23 ? ?
5-HT1A 3.571Partial agonist
5-HT1B 25737Partial agonist
5-HT1D 1662Partial agonist
5-HT2A 4.849Partial agonist
5-HT2B 7.10Silent antagonist
5-HT2C 480Silent antagonist
5-HT7 8–42 ? ?
α1A 3.50Silent antagonist
α1B 35 ? ?
α1D 3.9 ? ?
α2A 0.300Silent antagonist
α2B 0.450Silent antagonist
α2C 0.760Silent antagonist
α2D 1.5 ? ?
β1 661 ? ?
β2 20 ? ?
H1 339 ? ?
M1 >10,000 ? ?
Notes: All receptors are human except α2D-adrenergic, which is rat (no human counterpart), and 5-HT7, which was guinea pig. [4] [7]

Research

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. [8] In May 2008, terguride was granted orphan drug status for the treatment of pulmonary arterial hypertension. [9] In May 2010 Pfizer purchased worldwide rights for the drug. [10] However, development was discontinued in 2011.

See also

References

  1. ↑ "List of 5HT3 receptor antagonists (5hydroxytryptamine receptor antagonists)". Archived from the original on 2016-03-03.
  2. ↑ "Terguride - AdisInsight".
  3. ↑ Zajdel P, Bednarski M, Sapa J, Nowak G (April 2015). "Ergotamine and nicergoline - facts and myths". Pharmacol Rep. 67 (2): 360–3. doi:10.1016/j.pharep.2014.10.010. PMID   25712664. S2CID   22768662.
  4. 1 2 Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A (November 2002). "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". J Pharmacol Exp Ther. 303 (2): 791–804. doi:10.1124/jpet.102.039867. PMID   12388666. S2CID   6200455.
  5. ↑ Newman-Tancredi A, Cussac D, Audinot V, Nicolas JP, De Ceuninck F, Boutin JA, Millan MJ (November 2002). "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". J Pharmacol Exp Ther. 303 (2): 805–14. doi:10.1124/jpet.102.039875. PMID   12388667. S2CID   35238120.
  6. ↑ Newman-Tancredi A, Cussac D, Quentric Y, Touzard M, Verrièle L, Carpentier N, Millan MJ (November 2002). "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". J Pharmacol Exp Ther. 303 (2): 815–22. doi:10.1124/jpet.102.039883. PMID   12388668. S2CID   19260572.
  7. 1 2 "PDSP Database - UNC". pdsp.unc.edu. Archived from the original on 13 April 2021. Retrieved 15 January 2022.
  8. ↑ Janssen W, Schymura Y, Novoyatleva T, Kojonazarov B, Boehm M, Wietelmann A, et al. (2015). "5-HT2B receptor antagonists inhibit fibrosis and protect from RV heart failure". BioMed Research International. 2015: 438403. doi: 10.1155/2015/438403 . PMC   4312574 . PMID   25667920.
  9. ↑ Presseportal (Swiss press portal, in German)
  10. ↑ "TheDay.com 5/10/2010". Archived from the original on 2016-03-05. Retrieved 2010-05-21.
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