TASP0390325

TASP0390325 is a high affinity and orally active arginine vasopressin receptor 1B (V1B receptor) antagonist with antidepressant and anxiolytic activities[1].

Signaling Pathways >> GPCR/G Protein >> Vasopressin Receptor

Research Areas >> Neurological Disease

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].

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]. Animal Model: Male Sprague-Dawley (SD) rats (211-246 g)[1] Dosage: 0.3 and 1 mg/kg (TASP0390325 is suspended in 0.5% methylcellulose 400) Administration: Oral administration Result: Antagonized the increase in plasma ACTH levels induced by CRF/dDAVP in rats at a dose of 1 mg/kg. In contrast, 0.3 and 1.0 mg/kg itself did not significantly affect basal ACTH levels.

[1]. M Iijima, et al. Antidepressant and anxiolytic profiles of newly synthesized arginine vasopressin V1B receptor antagonists: TASP0233278 and TASP0390325. Br J Pharmacol. 2014 Jul;171(14):3511-25.

[2]. Kazumi Koga, et al. High-Contrast PET Imaging of Vasopressin V 1B Receptors with a Novel Radioligand, ¹¹C-TASP699. J Nucl Med. 2017 Oct;58(10):1652-1658.