AbstractReceptor binding studies revealed that flesinoxan potently and selectively binds to the 5‐HT1Areceptor (Ki= 1.7 nM). The anatomical distribution of [3H]‐flesinoxan binding sites is very similar to the localization of the 5‐HT1Asites labelled by [3H]‐8‐OH‐DPAT. In several functional models flesinoxan acted as a 5‐HT1Aagonist.Flesinoxan has been investigated in a variety of animal models predictive for anxiolytic activity. In a conflict test in pigeons, flesinoxan has potent anxiolytic activity at low doses (0.03–1 mg/kg i.m.). Flesinoxan is also highly active to reduce separation‐induced ultrasonic anxiety calls in infant rats and in an anticipatory anxiety model in adult mice. However, in the four‐plate test and the light‐dark model in mice, flesinoxan and other 5‐HT1Aagonists had no anxiolytic effects.Antidepressant properties of flesinoxan were shown in a behavioural despair model in rats: the forced‐swim test. Flesinoxan was more active (0.2–1.8 mg/kg s.c.) than classical tricyclic antidepressants. The putative antidepressant properties are also supported by the desensitisation of β‐adrenergic receptors in rats after subchronic administration of flesinoxan. In a functional test for β‐receptor activity in the brain (noradrenaline induced c‐AMP production in brain slices), a reduction of responsivity was observed after 2 weeks of treatment with flesinoxan (6 mg/kg/day).Therefore, based on the animal pharmacology there are strong indications that flesinoxan as a selective 5‐HT1Aagonist, has anxiolytic as wel