• Br. J. Pharmacol. · Sep 2013

    Pharmacological characterization of FE 201874, the first selective high affinity rat V1A vasopressin receptor agonist.

    • Rafik Marir, Anne Virsolvy, Kazimierz Wisniewski, Julie Mion, Dominique Haddou, Evelyne Galibert, Zahia Meraihi, Michel G Desarménien, and Gilles Guillon.
    • CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, F-34094, France; INSERM, U661, Montpellier, F-34094, France; Universités de Montpellier 1 & 2, UMR-5203, Montpellier, F-34094, France; Université Constantine 1, Faculté des sciences de la nature et de la vie, Constantine, Algérie.
    • Br. J. Pharmacol. 2013 Sep 1; 170 (2): 278-92.

    Background And PurposeDistinct vasopressin receptors are involved in different physiological and behavioural functions. Presently, no selective agonist is available to specifically elucidate the functional roles of the V1A receptor in the rat, one of the most widely used animal models. FE 201874 is a new derivative of the human selective V1A receptor agonist F180. In this study, we performed a multi-approach pharmacological and functional characterization of FE 201874 to determine whether it is selective for V1A receptors.Experimental ApproachWe modified an available human selective V1A receptor agonist (F180) and determined its pharmacological properties in cell lines expressing vasopressin/oxytocin receptors (affinity and coupling to second messenger cascades), in an ex vivo model (aorta ring contraction) and in vivo in rats (proliferation of adrenal cortex glomerulosa cells and lactation).Key ResultsFE 201874 exhibited nanomolar affinity for the rat V1A receptor; it was highly selective towards the rat V1B and V2 vasopressin receptors and behaved as a full V1A agonist in all the pharmacological tests performed. FE 201874 bound to the oxytocin receptor, but with moderate affinity, and behaved as an oxytocin antagonist in vitro, but not in vivo.Conclusions And ImplicationsOn functional grounds, all the data demonstrate that FE 201874 is the first selective agonist of the rat V1A receptor isoform available. Hence, FE 201874 may have potential as a treatment for the vasodilator-induced hypotension occurring in conditions such as septic shock and could be the most suitable compound for discriminating between the behavioural effects of arginine vasopressin and oxytocin.© 2013 The British Pharmacological Society.

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