tcsc0418 WAY-100635

WAY-100635 is a potent and selective 5-HT_1A Receptor antagonist with a pIC₅₀ of 8.87, an apparent pA₂ of 9.71.

IC50 & Target: pIC50 Value: 8.87 (5-HT_1A Receptor)^[1].

In Vitro: WAY-100635 is a potent and, at high concentrations, an insurmountable antagonist of the 5-HT_1A receptor agonist action of 5-carboxamidotryptamine, with an apparent pA₂ value (at 0.3 nM) of 9.71. WAY-100635 displaces specific binding of the 5-HT_1A radioligand, [³H]8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), to rat hippocampal membranes with a plC_IC50 of 8.87^[1].

In Vivo: Administration of (S)-WAY-100135 (0.025-1.0 mg/kg i.v.) moderately depresses neuronal activity at all doses tested. In contrast, administration of WAY-100635 (0.025-0.5 mg/kg i.v.) significantly increases neuronal activity. The stimulatory action of WAY-100635, like that of spiperone, is evident during wakefulness but not during sleep. Pretreatment with (S)-WAY-100135 (0.5 mg/kg i.v.) weakly attenuates the inhibitory action of 8-hydroxy-2-(di-n-propylamino) tetralin. In contrast, WAY-100635 at doses as low as 0.1 mg/kg i.v. completely blockes the action of 8-hydroxy-2-(di-n-propylamino) tetralin. The antagonist action of WAY-100635 at 5-HT_1A autoreceptors closely parallels its ability to increase neuronal activity. Overall, WAY-100635 appears to act as a selective 5-HT1A antagonist, whereas (S)-WAY-100135 does not. The results obtained with WAY-100635 confirm our previous findings obtained with spiperone and further support the hypothesis that 5-HT_1A autoreceptor-mediated feedback inhibition operates under physiological conditions^[2].