Amesergide

Amesergide (, ; developmental code name LY-237733) is a serotonin receptor antagonist of the ergoline and lysergamide families related to methysergide which was under development by Eli Lilly and Company for the treatment of a variety of conditions including depression, anxiety, schizophrenia, male sexual dysfunction, migraine, and thrombosis but was never marketed. It reached phase II clinical trials for the treatment of depression, erectile dysfunction, and premature ejaculation prior to the discontinuation of its development.

Pharmacology

Pharmacodynamics

Amesergide acts as a selective antagonist of the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors (K_i = 1.96–15.1 nM). It is also an antagonist of the serotonin 5-HT₇ receptor with relatively lower affinity (K_i = 78.0 nM). The drug is a potent antagonist of the α₂-adrenergic receptor in addition to the 5-HT₂ receptors via its major active metabolite 4-hydroxyamesergide (K_i = 13 nM). This profile of activity is similar to that of the so-called noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine (Remeron).

Amesergide also has affinity for the serotonin 5-HT_1D receptor (K_i = 57.9 nM) and lower affinity for the serotonin 5-HT_1A, α₁-adrenergic, and dopamine D₁ and D₂ receptors (K_i = 150–730 nM). It has negligible affinity for the histamine H₁ and muscarinic acetylcholine receptors (K_i > 10,000 nM). The drug does not appear to have been assessed at the serotonin 5-HT_1E, 5-HT_1F, 5-HT₄, 5-HT_5A, and 5-HT₆ receptors, nor at the dopamine D₃, D₄, and D₅ receptors.

See also

• Substituted lysergamide
• List of investigational antidepressants
• List of investigational sexual dysfunction drugs

References

External links

• Amesergide - Isomer Design
• Amesergide - AdisInsight