Is Ro 11-2465 (cyan-imipramine) an antagonist of postsynaptic serotonin receptors?
Ro 11-2465, a selective inhibitor of serotonin uptake of the imipramine group, was examined for its central and peripheral antiserotonin activity. Ro 11-2465 (10 mg/kg) antagonized the stimulation of the hind limb flexor reflex in the spinal rat evoked by serotonin agonists of direct mode of action (LSD, quipazine, m-chlorophenylpiperazine). However, in doses up to 20 mg/kg it did not inhibit the clonidine-induced stimulation of the flexor reflex. It also reduced the number of the quipazine-induced head twitches in rats (ID50 = 20.1 mg/kg) and, in doses 0.3--10.0 mg/kg, dose-dependently attenuated the pressor response to serotonin in the pithed rat. Like doxepine, amitriptyline, clomipramine and imipramine, Ro 11-2465 reduced the serotonin-induced contractions of the rat stomach fundus strip (its IC50 = 5 x 10(-5) M). The obtained results indicate that like other tricyclic inhibitors of serotonin uptake, Ro 11-2465 may also weakly block the postsynaptic serotonin receptors. Additional studies with fluoxetine and Org 6582 indicate that anti-serotonin properties of tricyclic compounds are not related to the serotonin uptake blocking properties.
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D002997:Clomipramine / Q000494:pharmacology; D006614:Hindlimb / Q000294:innervation; D007099:Imipramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology
D012702:Serotonin Antagonists; C024316:cianopramine; D000639:Amitriptyline; D011814:Quipazine; D008238:Lysergic Acid Diethylamide; D002997:Clomipramine; D007099:Imipramine