fluvoxamine and indalpine

Although relatively few drugs that specifically influence serotonin neurons have been used in humans, a wide variety of drugs has been used to modify serotonergic function in experimental animals. Several classes of agents increase serotonergic function. These include serotonin precursors (L-5-hydroxytryptophan and L-tryptophan) and monoamine oxidase inhibitors, which elevate serotonin stores; uptake inhibitors and releasers, which increase the concentration of serotonin in the synaptic cleft; and direct serotonin agonists, which mimic the action of serotonin on synaptic receptors. In addition, several kinds of drugs decrease serotonergic function, including serotonin depletors and agents that destroy serotonin neurons, as well as direct serotonin-receptor antagonists. The array of drugs now available improves the opportunities for clarifying the physiological roles of serotonin and gives promise of several therapeutic applications, including treatment of myoclonus.

Topics: Alanine; Brain; Citalopram; Clomipramine; Fenfluramine; Fluoxetine; Fluvoxamine; Humans; Monoamine Oxidase Inhibitors; Neurons; Oximes; p-Chloroamphetamine; Paroxetine; Piperidines; Propylamines; Receptors, Serotonin; Reserpine; Serotonin; Serotonin Antagonists; Synapses; Tetrabenazine; Zimeldine

Depression has been associated with a disturbance in serotonin function as reflected in platelet uptake of the transmitter as well as in CSF levels of its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA). CSF 5-HIAA levels are subnormal in approximately 30% of melancholia patients. Early studies suggested that patients with a disturbed serotonin metabolism were less responsive to treatment with uptake inhibitors with a preferential action on noradrenaline neurons. Such findings encouraged the search for compounds with a selective effect on serotonin neurons. Although some classical antidepressants are potent inhibitors of serotonin uptake, they are not selective, since their metabolites, which appear to have antidepressant effects, inhibit noradrenaline uptake. The consistent findings of an increased risk for suicide in patients with low CSF 5-HIAA underlines the importance of exploring drugs that act on serotonin transmission. The biochemical effects of some serotonin uptake inhibitors and their clinical and research potential in depression are reviewed.

Topics: 5-Hydroxytryptophan; Alanine; Citalopram; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Imipramine; Oximes; Paroxetine; Piperidines; Propylamines; Serotonin; Serotonin Antagonists; Trazodone; Zimeldine

In the treatment of depression, when antidepressant drug choice is made according to alterations of erythrocyte membrane transport of L-tyrosine and L-tryptophan in the individual patient, the clinical results are superior to those obtained when drugs are prescribed according to the physician's judgment. This is demonstrated by comparing three experimental groups: I, 100 patients treated in relation to their L-tyrosine and L-tryptophan transport; II, 30 patients treated according to the clinician's experience; III, 38 subjects treated against the L-tyrosine and L-tryptophan transport indications. In these groups, the frequency of patients improved by more than 70% is 77%, 47%, and 16%, respectively.

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder; Erythrocyte Membrane; Female; Fluvoxamine; Humans; Imipramine; Male; Mianserin; Middle Aged; Monoamine Oxidase Inhibitors; Oximes; Piperidines; Receptors, Adrenergic; Receptors, Serotonin; Tryptophan; Tyrosine

Reserpine + nialamid administration to the rat induces a strong yellow fluorescence of the neuronal bodies of the raphe, due to serotonin (5-HT) accumulation. Under these conditions, administration of clomipramine (an antidepressant drug acting preferentially on 5-HT-mediated neurons) induces a decrease of intraneuronal fluorescence and its interneuronal diffusion. On this pattern we administered new antidepressant drugs which act on 5-HT neurons in a much more intensive way than clomipramine (fluvoxamine, clovoxamine, LM 5008, citalopram, Ro 11-2465). To varying degrees, we observed in the raphe, in addition to a decrease in intraneuronal fluorescence and interneuronal diffusion, the presence of a yellow fluorescence in capillary walls. It seems that under these antidepressants, 5-HT, which is outside neuronal bodies because of uptake blockade, is partly caught by the capillary walls. In these walls rich in monoamine oxydase, 5-HT would be catabolized, 5HIAA dispersed in the blood and thus, this 'capillary effect' could correspond to a loss of 5-HT in the raphe. Antidepressant drugs preferentially acting upon noradrenaline (NA) neurons do not, in this model, induce analogous phenomena in NA cell bodies of the locus coeruleus. So the 'capillary effect' differentiates antidepressant drugs acting specifically on 5-HT or NA neurons. It may be considered together with other parameters which also indicate asymmetries on the modes of action of antidepressant drugs, such as effects on monoamine turnover (increase for NA and decrease for 5-HT) and on receptor sensitivity (decrease for NA and increase for 5-HT).

Topics: Animals; Antidepressive Agents, Tricyclic; Benzofurans; Brain Stem; Citalopram; Clomipramine; Ethers; Fluvoxamine; Imipramine; Indoles; Locus Coeruleus; Male; Microscopy, Fluorescence; Norepinephrine; Oximes; Piperidines; Propylamines; Raphe Nuclei; Rats; Receptors, Serotonin; Serotonin