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

This is a report of a controlled trial of gepirone, a 5-hydroxytryptamine (5-HT1A) partial agonist azapirone related to buspirone, in the treatment of atypical depression. The azapirones are of particular interest because their highly selective actions on the serotonergic system may possibly make them useful pharmacologic probes and potentially selective therapeutic agents. Sixty outpatients meeting Columbia criteria for definite or probable atypical depression were enrolled in a double-blind, randomized, placebo-controlled, 8-week clinical trial at a single site. The dosage schedule was fixed flexible, with 10-mg capsules given on a thrice-daily schedule, with doses of up to 120 mg daily. The response rate at 8 weeks for the intention-to-treat sample analyzed with the last observation carried forward was 62% (18 of 29 patients) for gepirone and 20% (6 of 30 patients) for placebo (chi 2 = 9.1; df = 1; p < 0.001). Robust and consistent drug-placebo differences are seen across virtually all rating scales post-treatment. The effect of gepirone was consistent across the levels of concomitant variables, including duration of episode and presence of dysthymia or panic. Gepirone is a novel antidepressant that holds promise for the treatment of atypical depression and that may be of heuristic value because of its relatively specific actions on the serotonergic system.
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PMID:Gepirone treatment of atypical depression: preliminary evidence of serotonergic involvement. 780 92

First defined as a residual diagnostic category in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), Generalized Anxiety Disorder (GAD) was until recently one of the least studied and least clearly conceptualized of the anxiety disorders. The clinical definition of GAD has however improved up to the fourth edition of the DSM where the disorder is now characterized as a chronic state of apprehensive expectation and uncontrollable worry concerning multiple daily life events or activities and accompanied with at least 3 symptoms belonging to a list of six common manifestations of psychic or motor tension. Clinical research demonstrating the stability and the specificity of somatic symptoms clearly support the validity of the diagnosis of GAD despite possible difficulties in the differential diagnosis with other chronic conditions or axis II disorders such as dysthymia or mixed anxiety-depressive disorder. After benzodiazepines (BZD) and 5-HT1A agonists like buspirone, several other types of new anxiolytic drugs have been developed for the treatment of GAD. Partial agonists at GABA-BZD receptor sites may offer the advantage of a better efficacy vs side-effects ratio over classical BZDs; however, systematic comparative clinical trials will have to demonstrate the clinical relevance of the encouraging results obtained with these drugs, at the experimental level, during studies in healthy volunteers and during the first placebo-controlled trials. Furthermore, the recent description of GABA-receptor's subunits clearly suggest that the development of drugs acting at this level and devoided of psychomotor or withdrawal side-effects is a target that is worth pursuing. On the other hand, the development of 5-HT2 and 5-HT3 antagonists is also of interest for the treatment of GAD since it could provide new anxiolytic drugs without these side-effects and thus easier to administer on a long-term basis corresponding to the chronicity of GAD. However, it will also be important to know if wether or not the efficacy of these new drugs, like that of buspirone, is associated with some effects on depressive symptomatology, develops only progressively over time and is different in previous BZD users compared to GAD patients who did not receive BZD before the new drug. Among these drugs in development for GAD, the most likely to reach the market in a near future are a BZD partial agonist (abecarnil), 5-HT1A agonists like ipsapirone and 5-HT3 antagonists like ondansetron. However, another area of new developments concerning the drug treatment of GAD is the use of antidepressants, which have demonstrated efficacy in this indication even in patients without depressive features or panic attacks symptoms. Considering the chronic nature of GAD, these drugs, like those acting on the 5-HT-system, would be more adapted than BZD for the long-term management of this condition. If confirmed by clinical trials involving antidepressants other than tricyclics, the efficacy of these drugs in GAD may suggest that common neurobiological mechanisms are involved in the pathogenesis of both anxiety and depressive disorders. Despite the potential interest of these new treatments of GAD, recent years have shown that the development of new anxiolytic drugs often appears limited by high-rates of placebo response in numerous clinical trials. This phenomenon may be related--in part--to the increasingly sophisticated designs used in such trials, such as extensive diagnostic workups, repeated evaluations and inclusion criteria selecting the less severe types of anxiety. As emphasized by other authors, much more research needs to be done to establish what effects various ways of conducting a trial have on the trial's results in order to facilitate the emergence of new psychopharmacological approaches in the treatment of GAD.
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PMID:[Treatment of generalized anxiety: new pharmacologic approaches]. 867 71

We evaluated the antidepressant-like effect of kaempferitrin (Km) isolated from the plant Justicia spicigera (Asteraceae), which is used in traditional medicine for relieving emotional disorders, such as "la tristeza" (sadness or dysthymia) and "el humor" (mood changes). The actions of Km were evaluated in a forced swimming test (FST) and a suspension tail test (TST) in mice. We explored the involvement of the serotonergic system and the hypothalamic-hypophysis-adrenal axis (HPA) in the antidepressant-like effect of Km. To evaluate nonspecific effects of Km on general activity, the open field test (OFT) was performed. Km at 5, 10, and 20 mg/kg induced an antidepressant-like effect. Sub-effective dose of Km (1 mg/kg) produced a synergistic effect with imipramine (6.25 mg/kg) and fluoxetine (10 mg/kg) but not with desipramine (3.12 mg/kg). Pretreatment with p-chlorophenylalanine methyl ester (PCPA), a serotonin synthesis inhibitor, N-{2-(4-(2-methoxyphenyl)-1-piperazinyl}-N-(2-pyridinyl)cyclohexecarboxamide (WAY-100635), a selective 5-HT1A receptor antagonist, and 8OH-DPAT, a selective 5-HT1A agonist, but not pindolol (10 mg/kg) blocked the anti- immobility effect induced by Km. Taken together, these results indicate that the antidepressant-like effect of Km is related to the serotonergic system, principally 5-HT1A. This effect was not related to changes in locomotor activity.
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PMID:Anti-depressant-like effect of kaempferitrin isolated from Justicia spicigera Schltdl (Acanthaceae) in two behavior models in mice: evidence for the involvement of the serotonergic system. 2553 42