Effects of the brain-penetrant and selective 5-HT6 receptor antagonist SB-399885 in animal models of anxiety and depression.
The effects of a selective 5-HT(6) receptor antagonist, SB-399885 (N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide), were evaluated in behavioural tests sensitive to clinically effective anxiolytic- and antidepressant-compounds using diazepam and imipramine as reference drugs. In the Vogel conflict drinking test in rats, SB-399885 (1-3mg/kg i.p.) caused an anxiolytic-like activity comparable to that of diazepam (2.5-5mg/kg i.p.). An anxiolytic-like effect was also seen in the elevated plus-maze test in rats, where SB-399885 (0.3-3mg/kg i.p.) was slightly weaker than diazepam (2.5-5mg/kg i.p.). In the four-plate test in mice, SB-399885 (3-20mg/kg i.p.) showed an anxiolytic-like effect which was weaker than that produced by diazepam (2.5-5mg/kg i.p.). In the forced swim test in rats, SB-399885 (10mg/kg i.p.) significantly shortened the immobility time and the effect was stronger than that of imipramine (30mg/kg i.p.). In the forced swim test in mice, SB-399885 (20-30mg/kg i.p.) had an anti-immobility action, comparable to imipramine (30mg/kg i.p.) and also in the tail suspension test in mice, SB-399885 (10-30mg/kg i.p.) had an antidepressant-like effect, though was weaker than imipramine (10-20mg/kg i.p.). The tested 5-HT(6) antagonist (3-20mg/kg i.p.) shortened the walking time of rats in the open field test and, at a dose of 30mg/kg i.p. reduced the locomotor activity of mice. SB-399885 (in doses up to 30mg/kg i.p.) did not affect motor coordination in mice and rats tested in the rota-rod test. Such data indicate that the selective 5-HT(6) receptor antagonist SB-399885had specific effects, indicative of this compound's anxiolytic and antidepressant potential.
Wesołowska
Anna
A
Department of New Drugs Research, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland. wesolow@if-pan.krakow.pl
Nikiforuk
Agnieszka
A
D000818:Animals; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D001362:Avoidance Learning / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002755:Choice Behavior / Q000187:drug effects; D003220:Conflict, Psychological; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use; D004327:Drinking Behavior / Q000187:drug effects; D004597:Electroshock; D019417:Hindlimb Suspension / Q000523:psychology; D007099:Imipramine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D013550:Swimming / Q000523:psychology
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D010879:Piperazines; D011985:Receptors, Serotonin; C503990:SB 399885; D012702:Serotonin Antagonists; D013449:Sulfonamides; C097216:serotonin 6 receptor; D007099:Imipramine; D003975:Diazepam