Selective Rat V1A Vasopressin Receptor Agonist: FE 201874's Pharmacological Profile and Therapeutic Potential

The study focuses on the exploration of vasopressin receptors' roles in physiological and behavioral functions. A derivative, FE 201874, of a human-specific V1A receptor agonist, F180, was synthesized to investigate its selectivity for V1A receptors in rats, a common animal model. The research involved modifying F180 to assess its pharmacological characteristics in various cell lines expressing vasopressin/oxytocin receptors, as well as its effects in an ex vivo model of aorta ring contraction and in vivo in rats, examining adrenal cortex glomerulosa cell proliferation and lactation.

Key findings indicate that FE 201874 has a nanomolar affinity for the rat V1A receptor and is highly selective against the rat V1B and V2 vasopressin receptors, functioning as a full V1A agonist in all conducted tests. It also binds to the oxytocin receptor with moderate affinity, acting as an antagonist in vitro but not in vivo.

The study concludes that FE 201874 is the first selective V1A receptor agonist for rats, suggesting its potential in treating vasodilator-induced hypotension in conditions like septic shock. It could also be instrumental in distinguishing the behavioral impacts of arginine vasopressin and oxytocin.