[18F]F15599, a novel 5-HT1A receptor agonist, as a radioligand for PET neuroimaging

Abstract

[(18)F]F15599 is a radiofluorinated agonist presenting interesting characteristics for probing in vitro and in vivo the high-affinity states of the 5-HT(1A) receptors. Its differential labelling of 5-HT(1A) receptors in vitro and in vivo may result from its reported preferential interaction with receptors coupled to specific G-protein subtypes.

Agonist and antagonist bind differently to 5-HT1A receptors during Alzheimer’s disease: A post-mortem study with PET radiopharmaceuticals

“…The neuropharmacological hypothesis of our study was that the agonist radiotracer Gpp(NH)p, confirming previous studies (Lemoine et al, 2010). In a recent study, we proposed that the coupling state of 5-HT 1A receptors was altered before the loss of receptors themselves in AD (Becker et al, 2014).…”

Radiosynthesis and Preclinical Evaluation of 18F-F13714 as a Fluorinated 5-HT1A Receptor Agonist Radioligand for PET Neuroimaging

“…The high affinity of F13714 is crucial because the specific binding of a radiotracer is a function of its affinity for the site relative to the density (Bmax) of that binding site. Therefore, an affinity lower than 1 nM would be desirable to achieve a good-contrast image for 5-HT 1A receptors (34).…”

Biased agonism at serotonin 5-HT1Areceptors: preferential postsynaptic activity for improved therapy of CNS disorders

“…In the case of F15599, a series of studies [98][99][100][101][102] have demonstrated that its distinctive 'signaling fingerprint' translates to a distinctive preferential activation of postsynaptic (mainly cortical) 5-HT 1A receptors, with less influence on presynaptic 5-HT 1A receptors. By contrast, F13714 exhibits an opposite preference, with more pronounced activation of 5-HT 1A autoreceptors and less potent activity at cortical receptors.…”