Terguride

Terguride (INNTooltip International Nonproprietary Name, JANTooltip 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]}

Terguride

Clinical data
Trade names	Teluron
Other names	Dironyl; 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	G02CB06 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Identifiers
IUPAC name 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	37686-84-3
PubChem CID	443951
IUPHAR/BPS	56
DrugBank	DB13399 Y
ChemSpider	392004
UNII	21OJT43Q88
KEGG	D01348 Y
CompTox Dashboard (EPA)	DTXSID3045809
ECHA InfoCard	100.048.732
Chemical and physical data
Formula	C20H28N4O
Molar mass	340.471 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCN(CC)C(=O)N[C@H]1C[C@H]2[C@@H](CC3=CNC4=CC=CC2=C34)N(C1)C
InChI 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)

Pharmacology

Pharmacodynamics

Terguride acts as an agonist of the dopamine D₂ receptor and as an antagonist of the serotonin 5-HT_2A and 5-HT_2B receptors, among other actions.^{[citation needed]}

As an antagonist of the 5-HT_2B receptor, terguride is not associated with cardiac valvulopathy.^[3]

Activities of terguride at various sites^[4][5][6][7]

Site	Affinity (Ki [nM])	Efficacy (Emax [%])	Action
D1	28	?	?
D2S	0.81	39	Partial agonist
D2L	1.1	0	Silent antagonist
D3	1.0	36	Partial agonist
D4	8.1	0	Silent antagonist
D5	23	?	?
5-HT1A	3.5	71	Partial agonist
5-HT1B	257	37	Partial agonist
5-HT1D	16	62	Partial agonist
5-HT2A	4.8	49	Partial agonist
5-HT2B	7.1	0	Silent antagonist
5-HT2C	48	0	Silent antagonist
5-HT7	8–42	?	?
α1A	3.5	0	Silent antagonist
α1B	35	?	?
α1D	3.9	?	?
α2A	0.30	0	Silent antagonist
α2B	0.45	0	Silent antagonist
α2C	0.76	0	Silent 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.

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. 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. "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.