Distinctive in vitro signal transduction profile of NLX‐112, a potent and efficacious serotonin 5‐HT1A receptor agonist

  title={Distinctive in vitro signal transduction profile of NLX‐112, a potent and efficacious serotonin 5‐HT1A receptor agonist},
  author={Adrian Newman-Tancredi and Jean Claude Martel and Cristina Cosi and Peter Heusler and Fabrice Lestienne and Mark A. Varney and Didier Cussac},
  journal={Journal of Pharmacy and Pharmacology},
NLX‐112 (befiradol, F13640) is a selective serotonin 5‐HT1A receptor agonist. Although it has been tested in vivo, little has been reported on its in vitro signal transduction profile. 

The selective 5-HT1A receptor agonist NLX-112 displays anxiolytic-like activity in mice

NLX-112 may possess anxiolytic properties which complement its known activity in models of movement disorders, and befiradol, a highly selective, potent and efficacious 5-HT1A receptor full agonist, may be associated with anxiety-like behaviours in mice.

From Receptor Selectivity to Functional Selectivity: The Rise of Biased Agonism in 5-HT1A Receptor Drug Discovery.

The results suggest that opportunities exist for innovative drug discovery of selective 5-HT1A receptor biased agonists that may open new avenues for the treatment of CNS disorders involving dysfunction of serotonergic neurotransmission.

In vivo biased agonism at 5-HT1A receptors: characterisation by simultaneous PET/MR imaging

Combined PET/fMRI represents a powerful tool in neuropharmacology, and opens new ways to address the concept of biased agonism by translational approaches, and demonstrates differential signalling by two 5-HT1A-biased agonists.



Signal transduction and functional selectivity of F15599, a preferential post‐synaptic 5‐HT1A receptor agonist

The signal transduction profile of F15599, a novel 5‐HT1A receptor agonist, is described, which suggests activation of post‐synaptic 5‐ HT1A receptors may provide enhanced therapy against depression.

Biased agonism at serotonin 5-HT 1A receptors: preferential postsynaptic activity for improved therapy of CNS disorders

‘biased agonists’ are desirable in order to preferentially activate receptor subpopulations in brain regions that mediate therapeutic activity, whilst avoiding those that control other effects.

Effector coupling mechanisms of the cloned 5-HT1A receptor.

Selective serotonin 5-HT1A receptor biased agonists elicitdistinct brain activation patterns: a pharmacoMRI study

This study revealed for the first time contrasting BOLD signal patterns of biased agonists in comparison to a classical agonist and a silent antagonist and offered functional information on the influence of pharmacological activation of 5-HT1A receptors in specific brain regions.

5-HT1A receptor activation and antidepressant-like effects: F 13714 has high efficacy and marked antidepressant potential.

Differential modulation by GTPγS of agonist and inverse agonist binding to h5‐HT1A receptors revealed by [3H]‐WAY100,635

GTPγS‐induced affinity changes of agonist and inverse agonist competition isotherms generally correlate well with ligand efficacy, with the notable exception of two chemically‐similar agents, S14506 and S14671, which are efficacious agonists, yet relatively insensitive to h5‐HT1A receptor/G‐protein coupling changes.

5-HT(1A) receptor activation: new molecular and neuroadaptive mechanisms of pain relief.

  • F. Colpaert
  • Biology
    Current opinion in investigational drugs
  • 2006
Chronic F-13640 administration causes an analgesia that surpasses that observed with morphine or other agents exemplifying other central nervous system drug mechanisms of pain relief, and may uniquely challenge the opioids for pain therapy.

Stimulated [35S]GTPγS binding by 5-HT1A receptor agonists in recombinant cell lines Modulation of apparent efficacy by G-protein activation state

G-protein activation by different 5-HT receptor ligands was investigated in h5-HT1A receptor-transfected C6-glial and HeLa cells using agonist-stimulated [35S]GTPγS binding to membranes in the presence of excess GDP, suggesting that the activity state of G-proteins can affect the maximal response.