Balovaptan is a Selective Brain-Penetrant Vasopressin 1a Receptor Antagonist

Arginine vasopressin (AVP) has three receptor subtypes: V1a, V1b, and V2 receptors. Specifically, the action of vasopressin is mediated by stimulating tissue-specific G protein-coupled receptor (GPCR). Besides, Gq/11 and V2 receptors activate V1a and V1b receptors of phospholipase, and interaction with GS activates adenylate cyclase. In mammals, V1aR and V1bR have related to blood pressure regulation and central feedback mechanisms. While V2R maintains water balance and electrolyte homeostasis.

Moreover, the neurohypophyseal hormone AVP is relevant to excessive physiological regulation. Usually, the main stimulants of vasopressin release are plasma tension, reduction of plasma volume or changes in blood pressure. They are mediated by arterial baroreceptors. Arginine vasopressin is a potentially important neurohormonal mediator in human heart failure (HF) syndrome and hyponatremia. Furthermore, Vasopressin affects the kidney’s treatment of free water, vasoconstriction and muscle cell biology. Here, we will introduce a selective brain-penetrant vasopressin 1a (hV1a) receptor antagonist, Balovaptan.

Balovaptan is a Selective Brain-Penetrant Vasopressin 1a (hV1a) Receptor Antagonist.

First of all, Balovaptan is an orally available V1a competitive antagonist with high specificity for V1a over V1b, V2. Importantly, Balovaptan has Kis of 1 and 39 nM for human (hV1a) and mouse (mV1a) receptors. Obviously, Balovaptan has the potential for the research of autism.

In the second place, Balovaptan shows >30000-fold selectivity for hV1a over hV2 receptors, 9891-fold selectivity over hOTR (human oxytocin receptor). Particularly, Balovaptan with 10 mg/kg by po has a Vss of 5.8 L/kg for mouse. Balovaptan with 2 mg/kg by iv has a CL of 91 mL/min·kg for mouse.

All in all, Balovaptan is an orally available, selective brain-penetrant vasopressin 1a (hV1a) receptor antagonist.


Ratni H, et al. J Med Chem. 2015 Mar 12;58(5):2275-89.