2. Academic Validation
  3. ST1936 stimulates cAMP, Ca2+, ERK1/2 and Fyn kinase through a full activation of cloned human 5-HT6 receptors

ST1936 stimulates cAMP, Ca2+, ERK1/2 and Fyn kinase through a full activation of cloned human 5-HT6 receptors

  • Eur J Pharmacol. 2011 Jul 1;661(1-3):8-14. doi: 10.1016/j.ejphar.2011.04.028.
Teresa Riccioni 1,  Fabio Bordi,  Patrizia Minetti,  Gilberto Spadoni,  Hyung-Mun Yun,  Bo-Hye Im,  Giorgio Tarzia,  Hyewhon Rhim,  Franco Borsini
Affiliations

Affiliation

  • 1 Sigma-tau Industrie Farmaceutiche Riunite S.p.A., Pomezia, Italy.
PMID: 21549693 DOI: 10.1016/j.ejphar.2011.04.028
Abstract

5-HT(6) receptor is one of the most recently cloned serotonin receptors, and it might play important roles in Alzheimer's disease, depression, and learning and memory disorders. Availability of only very few 5-HT(6) receptor agonists, however, does not allow examining their contribution in psychopharmacological processes. Therefore, a new 5-HT(6) receptor agonist, ST1936, was synthesized. ST1936 binds to human 5-HT(6) receptors with good affinity (K(i)=28.8 nM). ST1936 also exhibited some moderate binding affinity for 5HT(2B), 5HT(1A), 5HT(7) receptors and adrenergic α receptors. ST1936 behaved as a full 5-HT(6) agonist on cloned cells and was able to increase Ca(2+) concentration, phosphorylation of Fyn kinase, and regulate the activation of ERK1/2 that is a downstream target of Fyn kinase. These effects were completely antagonized by two 5-HT(6) receptor antagonists, SB271046 and SB258585. The other 5-HT(6) receptor agonist, WAY181187 also increased Fyn kinase activity. These results suggest that both ST1936 and WAY181187 mediate 5-HT(6) receptor-dependent signal pathways, such as cAMP, Fyn and ERK1/2 kinase, as specific agonists.

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