SERTINDOLE - A LIMBIC SELECTIVE NEUROLEPTIC WITH POTENT ANXIOLYTIC EFFECTS

The anxiolytic potential of the putative neuroleptic sertindole was assessed in various animal models of anxiety in rodents and in the marmoset human threat test. Sertindole facilitates the exploratory behaviour of mice and rats in the black and white two-compartment box over a large dose range. Sertindole is more potent than diazepam, i.e., minimal effective doses (MED) in the mouse are 0.00023 nmol (0.1 ng/kg) and 0.46 mu mol/kg (0.13 mg/kg), respectively, and MED in the rat are 0.23 nmol/kg (0.10 mu g/kg) and 35 nmol/kg (10 mu g/kg), respectively. Sertindole increases the time that pairs of rats spend in active social interaction (unfamiliar high light conditions) at extremely low doses (MED = 0.000023 nmol/kg [0.01 ng/kg]) being some 19 million-fold more active than diazepam (MED = 0.44 mu mol/kg; 0.13 mg/kg). Sertindole inhibits isolation-induced aggressive behaviour in the mouse, but only at high doses, and sertindole does not inhibit shock-induced suppression of drinking or footshock-induced ultrasonic vocalization in the rat. Sertindole similarly shows potent anxiolytic-like activity in the marmoset human threat test (MED = 23 nmol/kg; 10 mu g/kg). The range between anxiolytic doses and sedative doses is very large for sertindole, i.e., sedation is observed at 2,300 nmol/kg (1 mg/kg). (C) 1995 Wiley-Liss, Inc.