Effect of antidepressants on neuroendocrine axis in humans.
Unlike neuroleptic drugs, the effect of antidepressant drugs on the neuroendocrine axis in man is highly variable and may or may not be intimately related to their antidepressant action. However, the limited neuroendocrine data available does shed some light on the mechanism of action of these agents and raises some important questions, particularly about the regulation of PRL secretion and the interaction between various neurotransmitter systems. At one end of the spectrum, the ability of nomifensine and buproprion to lower serum PRL levels, presumably due to their ability to block the reuptake of DA by tuberoinfundibular DA neurons, suggests that it may be necessary to reconsider the conclusion that these neurons lack a DA reuptake mechanism or that these two agents are antidepressant by virtue of their ability to block DA uptake. Similarly, the inability of amphetamine or methylphenidate to decrease serum PRL levels in man suggests important differences between the tuberoinfundibular DA neurons in man and the rat. These findings also call into question the ability of these agents to block DA uptake or increase DA release in the tuberoinfundibular DA neurons. The finding that fluoxetine raises serum PRL levels, even in one subject, whereas zimelidine has not yet been shown to do so, and that fluoxetine does not potentiate the ability of 5-HTP to stimulate PRL secretion, has raised important questions about the role of 5-HT in PRL and GH regulation in man and the relationship between 5-HT and DA neurons in man. The occasional increase in serum PRL levels found in patients treated with lithium or the MAO inhibitor phenelzine are suggestive of important interindividual differences which may be revealed by neuroendocrine studies, differences which could be valuable in understanding the mechanism of action of these agents - e.g., does lithium decrease DA receptor sensitivity? - and fundamental aspects of neuroendocrine regulation - e.g., do the MAO inhibitors stimulate the production of a PRF? Further studies of the neuroendocrine effects of antidepressant treatments are clearly indicated. It is likely that such studies will enrich our understanding of how these agents work, of the difference between agents which have been classed together on the basis of preclinical studies (e.g., DMI, which appears to increase PRL and GH, and NT which appears not to) and provided additional evidence to test current hypotheses about the biological basis of their antidepressant action.
D000657:Amoxapine / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D006728:Hormones / Q000097:blood*; D006801:Humans; D008094:Lithium / Q000494:pharmacology; D008803:Mianserin / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology
D000928:Antidepressive Agents; D003984:Dibenzazepines; D006728:Hormones; D008996:Monoamine Oxidase Inhibitors; D018377:Neurotransmitter Agents; D012702:Serotonin Antagonists; D008803:Mianserin; D011388:Prolactin; D008094:Lithium; D000657:Amoxapine; D004298:Dopamine; D009638:Norepinephrine