Effect of nomifensine on central 5-hydroxytryptamine neurons.
Effects of nomifensine (8-amino-1, 2, 3, 4-tetrahydro-2-methyl-4-phenyl-isoquinoline) (NF), an antidepressant drug which inhibits dopamine uptake, on central serotonergic structures were studied in rats. NF affects of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid levels in the whole brain as well as in the separate rat brain structures. The 5-HT turnover is decreased in the whole brain and the striatum but increased in the midbrain and the hippocamp as judged from experiments with tryptophan hydroxylase inhibitor, alpha-propyldopacetamide. Pretreatment with dopamine-receptor blocking agent, spiperone, antagonized the increase of 5-HT turnover rate in brain regions mentioned above. NF stimulates the hind limb flexor reflex in spinal rat, a preparation regarded as a model for evaluation of drug action on central 5-HT neurons. This stimulatory effect was antogonized by cyproheptadine, by reserpine and imipramine. The obtained results indicate that NF activates central 5-HT neurons both directly and indirectly, via stimulation of dopamine receptors as described previously for other dopamine agonists.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*
D007546:Isoquinolines; D011954:Receptors, Dopamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid