Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two approaches have been followed in attempting to elucidate the mechanisms of action of antidepressants. The first involves studies on the chronic effects of antidepressants and ECT on neurotransmitter receptor function in the rat brain. Such studies suggest that antidepressants decrease alpha 2 and beta-adrenoceptor function, increase alpha 1 receptor function, reduce 5-HT1A and dopamine autoreceptor function and increase GABA B function; changes also occur in 5-HT2 receptor function with antidepressants decreasing while ECT increases the activity of these receptors. The second approach involves studying platelets, lymphocytes and amine metabolites in the body fluids of depressed patients before and following effective treatment. Results of these studies suggest that while alpha-adrenoreceptors are largely unchanged, beta-receptors are increased and 5-HT2 receptors decreased in the depressed patient but normalise following effective treatment irrespective of the type of treatment. Such findings emphasize the importance of receptor adaptations in evaluating the mode of action of antidepressant treatments.
 ...
PMID:Antidepressants. Current concepts of mode of action. 167 87

Hypotheses of antidepressant action which argue that even norepinephrine (NE) uptake inhibitors ultimately work through potentiation of serotonergic function are critically reviewed. Preclinical electrophysiologic data can be interpreted as evidence for enhanced serotonin (5-HT) throughput as a common mechanism of action of all antidepressants. Biochemical data in rats (e.g., microdialysis) and humans (e.g., opposite effects of ECT on 5-HIAA in cerebrospinal fluid), however, suggest that more is involved than simply enhanced 5-HT function when NE uptake inhibition is combined with 5-HT uptake inhibition. The case, however, for noradrenergic effects on 5-HT function is quite strong either with regard to stimulation of alpha 1 receptors on 5-HT cell bodies or alpha 2 heteroreceptors on 5-HT nerve endings. Even the reported ability of pindolol to potentiate the antidepressant effects of 5-HT uptake inhibitors may prove to involve noradrenergic effects and not simply antagonism of 5-HT1A receptors as currently hypothesized. The biochemically specific drugs needed to directly test these concepts are not yet available. On the other hand, compounds which combine noradrenergic and serotonergic effects (e.g., alpha 2 antagonism and 5-HT2 antagonism) that go beyond those of the classic uptake inhibitors are emerging as agents to test the clinical potential of selective manipulation of these interacting neurotransmitter systems.
 ...
PMID:Adrenoceptors and serotonin receptor function: relevance to antidepressant mechanisms of action. 863 64

In our previous positron emission tomography (PET) study, we demonstrated that ECT decreased dopamine D2 receptor in major depressive disorder (MDD). Although many animal studies have focused on the effect of ECT on serotonergic neurotransmission, no human study has directly examined the effect of ECT on brain serotonin [5-hydroxytryptamine (5-HT)] 1A receptors (5-HT1ARs). Using PET with [11C]WAY 100635, we aimed to evaluate the effect of ECT on 5-HT1ARs in patients with MDD. Nine patients underwent PET scans before and after a series of 6-7 bilateral ECTs. Region-of-interest analysis was performed based on the simplified reference tissue model. There were no significant changes in 5-HT1AR binding in patients between before and after ECT. ECT did not alter [11C]WAY 100635 binding even after recovery from depressive episode. Although the present finding does not exclude the involvement of brain 5-HT1A systems in the antidepressant action of ECT, it may indicate the involvement of other neurotransmission mechanisms.
 ...
PMID:Effect of electroconvulsive therapy on 5-HT1A receptor binding in patients with depression: a PET study with [11C]WAY 100635. 2006 60