Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 50 (20), 5024-33

High-efficacy 5-HT1A Agonists for Antidepressant Treatment: A Renewed Opportunity

Affiliations

High-efficacy 5-HT1A Agonists for Antidepressant Treatment: A Renewed Opportunity

Jean Louis Maurel et al. J Med Chem.

Abstract

We report the discovery of novel 5-HT1A receptor agonists and describe the process that led to the antidepressant candidate 9 (F 15599). 9 has nanomolar affinity for 5-HT1A binding sites and is over 1000-fold selective with respect to the other 5-HT1 receptor subtypes, 5-HT2-7 receptor families, and also numerous GPCRs, transporters, ion channels, and enzymes. In a cellular model of signal transduction, 9 activates h5-HT1A receptors with an efficacy superior to that of the prototypical 5-HT1A agonist (+/-)-8-OH-DPAT and comparators undergoing clinical trials. After acute oral administration in rats, 9 totally reverses immobility in the forced swimming test and produces behaviors characteristic of 5-HT1A receptor activation. However, these effects occurred at widely separated doses, suggesting that 9 discriminates between distinct populations of 5-HT1A receptors. While the clinical relevance of these observations is still unknown, this opens new perspectives for the treatment of depressive disorders.

Similar articles

See all similar articles

Cited by 16 PubMed Central articles

See all "Cited by" articles

Substances

LinkOut - more resources

Feedback