Terguride

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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.Script error: No such module "Unsubst".

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.Script error: No such module "Unsubst".

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]
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.

See also

References

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  9. Presseportal (Swiss press portal, in German)
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