TASP0390325

TASP0390325 is a high affinity and orally active arginine vasopressin receptor 1B (V1B receptor) antagonist with antidepressant and anxiolytic activities^[1]. In Vitro: TASP0390325 shows a high affinity and potent antagonist activity for V1B receptors^[1].
TASP0390325 dose-dependently inhibits [³H]-AVP binding to recombinant human V1B receptors with the IC₅₀ value of 2.72 nM^[1].
TASP0390325 also inhibits [³H]-AVP binding to rat anterior pituitary membranes, with the IC₅₀ value of 2.22 nM^[1].
TASP0390325 potently attenuates the 2.5 nM AVP-induced increase in [Ca²⁺]_i, with IC₅₀ values of and 20.2 nM^[1].
Pretreatment with TASP0390325 inhibits the retention of ¹¹C-TASP699 in a dose-dependent manner. Binding of ¹¹C-TASP699 to monkey pituitary slices is specifically localized to the anterior lobe. The radioligand binding is inhibited by TASP0390325 in a concentration-dependent manner. The IC₅₀ value of TASP0390325 is 2.16 nM^[2]. In Vivo: TASP0390325 blocks the anterior pituitary V1B receptor in vivo. Oral administration of TASP0390325 antagonized the increase in plasma ACTH levels induced by CRF/dDAVP in rats, indicating that TASP0390325 blocks the anterior pituitary V1B receptor in vivo. TASP0390325 (1 mg/kg) significantly antagonizes CRF/dDAVP-induced plasma ACTH in rats^[1].
Oral administration of TASP0390325 also exerts antidepressant effects in two models of depression (a forced swimming test and an olfactory bulbectomy model)^[1].