Summary
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 (10mg/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, dosedependently 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 (itsIC50=5×10−5M).
The obtained results indicate that like other tricyclic inihibtors 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.
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Pawlowski, L., Kwiatek, H. & Górka, Z. Is Ro 11-2465 (Cyan-imipramine) an antagonist of postsynaptic serotonin receptors?. J. Neural Transmission 52, 61–72 (1981). https://doi.org/10.1007/BF01253098
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DOI: https://doi.org/10.1007/BF01253098