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Sertindole: A limbic selective neuroleptic with potent anxiolytic effects
Author(s) -
Sánchez Connie,
Arnt Jørn,
Costall Brenda,
Domeney Annette M.,
Kelly Elisabeth,
Naylor Robert J.
Publication year - 1995
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430340104
Subject(s) - sertindole , pharmacology , anxiolytic , diazepam , marmoset , sedative , chemistry , sedation , endocrinology , medicine , anxiety , haloperidol , psychiatry , biology , dopamine , paleontology
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 μmol/kg (0.13 mg/kg), respectively, and MED in the rat are 0.23 nmol/kg (0.10 μg/kg) and 35 nmol/kg (10 μg/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 μmol/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 footschock‐induced ultrasonic vocalization in rat. Sertindole similarly shows potent anxiolytic‐like activity in the marmoset human threat test (MED = 23 nmol/kg; 10 μg/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). © Wiley‐Liss, Inc.