Clinical neuropharmacology
-
Clin Neuropharmacol · Jan 1993
Randomized Controlled Trial Comparative Study Clinical TrialDownregulation of serotonin receptor subtypes by nortriptyline and adinazolam in major depressive disorder: neuroendocrine and platelet markers.
Neuroendocrine and platelet markers of serotonin (5-hydroxytryptamine, 5-HT) receptor functioning are useful tools for studying the downregulation of 5-HT receptors, a leading hypothesis for the mechanism of action of antidepressant drugs. The 5-HT releaser fenfluramine raises body temperature as well as plasma concentrations of ACTH, cortisol, and prolactin. Pretreatment with the 5-HT1 antagonist pindolol did not block the hyperthermic response to fenfluramine, mediating its actions via non-5-HT1 receptor subtypes (presumably 5-HT2/1C). ⋯ IC50 values for ketanserin inhibition of 5-HT-induced platelet shape change response, a marker of 5-HT2/1c receptors, were elevated after nortriptyline treatment in depressed patients, and this increase could be accounted for by those subjects who responded well to antidepressant treatment. Adinazolam treatment did not alter the platelet shape change response. Our data suggest that downregulation of 5-HT2/1c receptors may be linked to the clinical response of depressed patients treated with nortriptyline.
-
Clin Neuropharmacol · Jan 1993
Review Comparative StudyNovel serotonergic mechanisms and clinical experience with nefazodone.
Chronic administration of antidepressant drugs enhances synaptic serotonergic transmission. Nefazodone, a member of a new class of antidepressants, has a pharmacologic profile that is distinct from the first-generation agents (e.g., tricyclics and monoamine oxidase inhibitors) as well as the more selectively acting second-generation agents (e.g., serotonin or norepinephrine uptake inhibitors, and serotonin type 1A partial agonists). Nefazodone acts both as a 5-HT2 receptor antagonist and as a serotonin (5-HT) reuptake inhibitor. ⋯ In placebo-controlled studies comparing nefazodone and the tricyclic antidepressant imipramine, the drugs produced comparable and significant therapeutic benefit. Nefazodone is associated with fewer adverse events than imipramine. Nefazodone lacks the troublesome anticholinergic side effects of tricyclic antidepressants, as well as serotonergic/noradrenergic-mediated effects.(ABSTRACT TRUNCATED AT 250 WORDS)
-
Clin Neuropharmacol · Jan 1993
ReviewSerotonin receptor subtypes in depression: evidence from studies in neuroendocrine regulation.
Serotonin (5-HT) neuroendocrine tests are a valid and acceptable means of measuring 5-HT neurotransmission in humans. Recently, the availability of selective 5-HT receptor ligands has allowed the assessment of specific 5-HT receptor subtype function using neuroendocrine methods. ⋯ In contrast, endocrine responses to direct 5-HT1A and 5-HT2/1C receptor agonists are not consistently attenuated in depressed patients. The current data suggest that depressive illness is associated with an impairment of 5-HT neurotransmission that involves decreased 5-HT release rather than altered sensitivity of postsynaptic 5-HT receptors.