In a non-clinical PET study 
using [11C]WAY-100635, preferential binding of pindolol to 5-HT1A autoreceptors was observed [19], but this was inconsistent with the conclusions of an ex vivo autoradiography (ARG) review that used intravenous administration of [3H]WAY-100635 and recognized nonselective binding of pindolol to five-HT1A receptors in rat mind [20]. Wf-516 (structural formula: (2 S)-one-[4-(three,four-dichlorophenyl)piperidin-one-yl]-3-[two-(5-methyl-1,three,4-oxadiazol-2-yl)benzo[b]furan-4yloxy]propan-2-ol monohydrochloride), a novel investigational antidepressant with high affinity for five-HTT and five-HT1A receptors [21], has been proven to have a lot more quick antidepres-sant-like results than the classical tricyclic antidepressant imipramine in a rat continual gentle pressure model of melancholy [22]. Moreover, a recent in vivo electrophysiological review utilizing rats has indicated that Wf-516 at low and medium doses was an antagonist for presynaptic but not EPZ020411 (hydrochloride) postsynaptic five-HT1A receptors [23]. Even though our earlier PET examine of rats shown in vivo binding of Wf-516 to central five-HTTs in a dosedependent manner [24], the pharmacological mechanisms involved in the presynaptic/postsynaptic selectivity of binding of Wf-516 to five-HT1A receptors in residing brains experienced nonetheless remained to be clarified employing neuroimaging assays. The current review was performed in buy to establish the properties of the conversation in between Wf-516 and presynaptic and postsynaptic 5-HT1A receptors localized predominantly in the raphe nucleus and hippocampus, respectively. Occupancies of these receptors by Wf-516 and pindolol had been measured and in contrast in rat brains using PET with [11C]WAY-100635, and presynaptic selectivity of Wf-516 was even more examined by treating rats with a toxin for five-HT neurons.Figure one. Binding affinities of Wf-516 and pindolol for central 5-HT1A receptors quantified by in vitro ARG. (A) Consultant autoradiograms displaying distribution and intensity of [11C]WAY-100635 radiosignals in rat mind sections containing the hippocampus (arrows) and raphe nucleus (arrowhead) and its attenuation by diverse concentrations of Wf-516 or pindolol. (B) Inhibition curves of [11C]WAY-100635 binding to the hippocampus (shut symbols) and raphe nucleus (open symbols) by Wf-516 (left) and pindolol (proper). Bars show S.E. (n = 3).Determine two. Occupancies of 5-HT1A receptors16397257 by Wf-516 and pindolol assessed by ex vivo ARG. (A) Consultant autoradiograms showing distribution and depth of [11C]WAY-100635 radiosignals in rat brain sections made up of the hippocampus (arrows) and raphe nucleus (arrowhead) after oral administration of Wf-516 and intraperitoneal administration of pindolol.
