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.