Anxiolytic-like actions of anpirtoline in a mouse light-dark aversion paradigm.
The anxiolytic-like potential of anpirtoline was assessed in a mouse light/dark aversion test. Anpirtoline (1.0 ng kg(-1)-1.0 micrograms kg-1 i.p.) reduced the aversive responding of mice. This was detected as an increase in the latency to locate the non-aversive compartment and by decreases in the percentage of the time spent in the dark compartment, and the numbers of rears and line crossings in the dark compartment. In radioligand binding studies anpirtoline displayed submicromolar affinity for 5-HT1A, 5-HT1B and 5-HT3 receptor recognition sites (Ki = 151, 28 and 30 nM, respectively) and more modest affinity for 5-HT2 receptor recognition sites (Ki = 1.48 microM). It is concluded that anpirtoline has a unique spectrum of affinity for 5-HT receptor subtypes, its interaction with which may account for its anxiolytic-like activity.
Metzenauer
P
P
ASTA Pharma Aktiengesellschaft, Frankfurt, Germany.
Barnes
N M
NM
Costall
B
B
Gozlan
H
H
Hamon
M
M
Kelly
M E
ME
Murphy
D A
DA
Naylor
R J
RJ
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D003624:Darkness; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D008027:Light; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D010880:Piperidines; D011725:Pyridines; D011985:Receptors, Serotonin; C075631:anpirtoline