ArticleBritish journal of pharmacology2009
Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1A receptor agonist.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Role of 5-HTBiomolecules · 2025Pooled it
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- Discovery of NLX-266, an Orally Available and Metabolically Stable ERK1/2-Biased 5-HTJournal of medicinal chemistry · 2025Article
- Acute administration of NLX-101, a Serotonin 1A receptor agonist, improves auditory temporal processing during development in a mouse model of Fragile X Syndrome.Journal of neurodevelopmental disorders · 2025Article
- The 5-HTPsychopharmacology · 2023Article
- GMolecular pharmacology · 2023Article
- The Serotonin 1A (5-HTCNS drugs · 2023Review
- Neural serotonergic circuits for controlling long-term voluntary alcohol consumption in mice.Molecular psychiatry · 2022Article
- Molecular Signaling Mechanisms for the Antidepressant Effects of NLX-101, a Selective Cortical 5-HTPharmaceuticals (Basel, Switzerland) · 2022Article
- Novel Molecular Targets of Antidepressants.Molecules (Basel, Switzerland) · 2022Review
- Update on GPCR-based targets for the development of novel antidepressants.Molecular psychiatry · 2022Review
- Serotonergic-Muscarinic Interaction within the Prefrontal Cortex as a Novel Target to Reverse Schizophrenia-Related Cognitive Symptoms.International journal of molecular sciences · 2021Article
- The selective 5-HTPsychopharmacology · 2021Article
- Ketamine: A tale of two enantiomers.Journal of psychopharmacology (Oxford, England) · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Discovery of Novel pERK1/2- or β-Arrestin-Preferring 5-HTJournal of medicinal chemistry · 2020Article
- (ACS pharmacology & translational science · 2020Article
- Advances in simultaneous PET/MR for imaging neuroreceptor function.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Review
- Pharmacological Studies on the Role of 5-HTFrontiers in behavioral neuroscience · 2020Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeActivation of post-synaptic 5-HT(1A) receptors may provide enhanced therapy against depression. We describe the signal transduction profile of F15599, a novel 5-HT(1A) receptor agonist. EXPERIMENTAL APPROACH: F15599 was compared with a chemical congener, F13714, and with (+)8-OH-DPAT in models of signal transduction in vitro and ex vivo. KEY
resultsF15599 was highly selective for 5-HT(1A) receptors in binding experiments and in [(35)S]-GTPgammaS autoradiography of rat brain, where F15599 increased labelling in regions expressing 5-HT(1A) receptors. In cell lines expressing h5-HT(1A) receptors, F15599 more potently stimulated extracellular signal-regulated kinase (ERK1/2) phosphorylation, compared with G-protein activation, internalization of h5-HT(1A) receptors or inhibition of cAMP accumulation. F13714, (+)8-OH-DPAT and 5-HT displayed a different rank order of potency for these responses. F15599 stimulated [(35)S]-GTPgammaS binding more potently in frontal cortex than raphe. F15599, unlike 5-HT, more potently and efficaciously stimulated G(alphai) than G(alphao) activation. In rat prefrontal cortex (a region expressing post-synaptic 5-HT(1A) receptors), F15599 potently activated ERK1/2 phosphorylation and strongly induced c-fos mRNA expression. In contrast, in raphe regions (expressing pre-synaptic 5-HT(1A) receptors) F15599 only weakly or did not induce c-fos mRNA expression. Finally, despite its more modest affinity in vitro, F15599 bound to 5-HT(1A) receptors in vivo almost as potently as F13714. CONCLUSIONS AND IMPLICATIONS: F15599 showed a distinctive activation profiles for 5-HT(1A) receptor-mediated signalling pathways, unlike those of reference agonists and consistent with functional selectivity at 5-HT(1A) receptors. In rat, F15599 potently activated signalling in prefrontal cortex, a feature likely to underlie its beneficial effects in models of depression and cognition.
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