The effect of DAU 6215, a novel 5HT-3 antagonist, in animal models of anxiety.
The aim of the present study was to evaluate the effect of DAU 6215 (N-(endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2, 3-dihydro-2-oxo-1H-benzimidazol-1-carboxamide, hydrochloride), which is a 5HT-3 receptor antagonist, chemically different from the other 5HT-3 antagonists, on a wide variety of animal models sensitive to anxiolytics. Nine animal models were used. DAU 6215 was active in reducing (i) aversion to a brightly lit environment in the light/dark exploratory test in mice, (ii) unpleasant properties of an aversive drug in rats (naloxone-induced place aversion), and (iii) aggressiveness in monkeys. DAU 6215 was effective at doses ranging (a) between 10 and 1000 micrograms/kg given i.p. in mice, (b) between 15 and 30 micrograms/kg given s.c. in rats and (c) between 1 and 10 micrograms/kg given orally in monkeys. DAU 6215 was inactive in (iv) the elevated plus maze, (v) conflict test and (vi) emotional hypophagia in rats and in (vii) the four plates test, (viii) staircase test and (ix) stress-induced hyperthermia in mice. Diazepam was active in all tests. In contrast to diazepam, DAU 6215 did not induce place preference, suggesting the possible lack of addictive properties.
Borsini
F
F
Boehringer Ingelheim Italia S.p.A., Milano.
Brambilla
A
A
Cesana
R
R
Donetti
A
A
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004195:Disease Models, Animal; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D001562:Benzimidazoles; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D012702:Serotonin Antagonists; C070191:itasetron