Effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on 5-HTP-induced head shaking and behavioral symptoms induced by 5-methoxy-N,N,dimethyltryptamine in rats: comparison with some other 5-HT receptor antagonists.

Two drugs, ICS 205-930 and MDL 72222, which block a specific serotonin receptor subtype (5-HT3), were tested for their ability to reduce certain behaviors in rats. They reduced head shaking caused by L-5-HTP, but were at least 600 times less potent than pirenperone and ketanserin, and at least 50 times less potent than methysergide. They were more than 1000 times less potent than pirenperone or methysergide, and 100 times less potent than ketanserin, in blocking forepaw treading and tremor caused by 5-MeODMT. These results indicate that ICS 205-930 and MDL 72222 do not substantially interact with 5-HT2 receptors in the brain and lack significant blocking activity at the serotonin receptors responsible for the behavioral effects of 5-MeODMT.

Study at a glance

Abstract

The effect of the selective 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 on head shaking behavior induced by L-5-HTP and behavioral symptoms induced with 5-methoxy-N,N,-dimethyltryptamine (5-MeODMT) in rats was evaluated. Both drugs dose-dependently reduced L-5-HTP-induced head shaking but were at least 600 times less potent than pirenperone and ketanserin and at least 50 times less potent than methysergide. ICS 205-930 and MDL 72222 were more than 1000 times less potent than pirenperone or methysergide and 100 times less potent than ketanserin in blocking 5-MeODMT-induced forepaw treading and tremor. Since it appears that head shakes induced by L-5-HTP are mediated by 5-HT2 receptors, these data suggest that ICS 205-930 and MDL 72222 do not significantly interact with 5-HT2 receptors in the brain. Furthermore, the data suggest that ICS 205-930 and MDL 72222 lack appreciable antagonistic activity at the 5-HT receptor(s) mediating those behavioral effects induced by 5-MeODMT.