AVPR modulators(Universitat Autònoma de Barcelona)

Distinct 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.

We 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).

FE 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.

On 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.

In this paper, the acute toxicity of four fuel oils including F120, F180, F380 and No.-20 was evaluated by exposing the marine microalgae Chlorela spp. (Chlorophyta) and Skeletonema costatum (Bacillariophyta) in the fuel oil water accommodated fractions (WAF). The bioassay showed that F180 WAF was the most toxic to both microalgae. The 96 h EC(50) value of F180 WAF for Skeletonema costatum and Chlorela spp. was 9.41 and 13.63 mg/L expressed in concentration of total petroleum hydrocarbons, respectively. WAFs of F120, F180 and F380 were more toxic to Skeletonema costatum than to Chlorela spp. In contrast, No.-20 WAF did not show significant toxicity for both Skeletonema costatum and Chlorela spp.