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)

The role of serotonin in psychiatry has been the focus of speculation for several decades. The literature since 1966 is reviewed (and referenced) and five organizing questions are identified: (1) What are the major hypotheses regarding the involvement of the serotonin system in panic disorder? (2) Is there a serotonin system defect associated with panic disorder? (3) Is a serotonin system defect the cause of panic disorder? (4) Are the 5-HT1A agonists and the 5-HT2 antagonists effective in this condition? (5) Are serotonin selective uptake inhibitors (SSUIs) effective in panic disorder via the serotonin system or some other mechanism? Though the role of the serotonin system in panic disorder and social phobia is uncertain there is increasing agreement that SSUIs effectively treat panic disorder but further double-blind placebo-controlled studies are needed.
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PMID:Serotonin in panic disorder and social phobia. 791 Nov 42

Social phobia is a common anxiety disorder that is underdiagnosed and undertreated. To date, three classes of serotonin drugs have been used to treat patients suffering from social phobia. These include the serotonin selective reuptake inhibitors (SSRIs), the partial 5-HT1A agonist buspirone, and the 5-HT3 antagonist ondansetron. Although none of the serotonin agents have yet been directly compared with the gold standard monoamine oxidase inhibitor phenelzine or the high potency triazolobenzo-diazepines alprazolam or clonazepam, the SSRIs, as a class, appear to be clinically useful agents. Further studies using larger sample sizes and double-blind methodology are needed to clarify the role of serotonin drugs in the treatment of social phobia.
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PMID:Role of serotonin drugs in the treatment of social phobia. 918 26

In recent years generalised anxiety disorder (GAD) has become a much better defined disorder, with specific criteria distinguishing it from the other anxiety disorders; however, it still lacks the same public and scientific interests as some of the other anxiety disorders such as panic and social phobia. Nevertheless, refinement in the treatment of GAD is becoming more evident through the conduct of clinical trials. Up until the mid-1980's, treatment consisted primarily of benzodiazepines. However, as a result of growing characterisation of their abuse potential, other therapeutic options were explored. Benzodiazepines became seen as an effective short-term therapy, and buspirone and some of the newer antidepressants have become the treatment of choice for patients with GAD requiring long-term treatment. Buspirone was the first available alternative to the benzodiazepines in the US; however, the initial excitement over this agent was somewhat dampened because of its mild efficacy combined with a slow onset of action. The antidepressants were seen as beneficial for the treatment of GAD because of the high comorbidity with depression, thus allowing a better outcome for these patients. The antidepressants that offer both a good adverse effect profile and efficacy are the selective serotonin reuptake inhibitors including paroxetine, and the serotonin-norepinephrine reuptake inhibitors such as venlafaxine. Clinicians should also consider the potential benefits of psychotherapy as an adjunct to medication. There are a number of potentially new pharmacotherapies being investigated, including newer serotonin 5-HT1A receptor agonists, cholecystokinin receptor antagonists, neurokinin receptor antagonists, gabapentin and its analogues, and gamma-aminobutyric acid (GABA)A receptor modulators. However, these compounds are all in the early stages of investigation, and there are no new therapies expected to be released in the near future. Nonetheless, in the search for the ideal anxiolytic, a more positive outlook is allowed by imminent future research for new treatment options in patients with GAD.
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PMID:Generalised anxiety disorder: treatment options. 1210 25

Since the introduction of SSRIs, pharmacotherapy for anxiety disorders has significantly changed. Although the SSRIs are considered to be a first-line treatment for the most of anxiety disorders benzodiazepines are still widely used in clinical practice despite the risk of dependence and strong recommendation for their use as a second-line. The SSRIs only replaced tricyclic antidepressants and the MAO inhibitors especially in the treatment of panic disorder, obsessive-compulsive disorder and social phobia. Combination of the SSRIs and the benzodiazepines is widely used. Recently it has been suggested that the combination of SSRI and benzodiazepine is rational, because each drug has a different mechanism of action, the benzodiazepines enhancing GABAergic transmission, and the SSRIs stimulating the 5-HT1A receptor that may inhibit the postsynaptic neuronal excitability in the amygdala and the prefrontal cortex that comprise the brain circuit of fear and anxiety. Recent imaging studies suggested the hyperactivity of the amygdala in the patients with generalized social anxiety disorder and successful treatment with cognitive behavioral therapy or SSRI might significantly reduce the hyperactivity of the amygdala. It was suggested that the rational combination of SSRIs and benzodiazepines seems to be an effective and practical way of treatment for most anxiety disorders.
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PMID:[Recent trends in pharmacotherapy for anxiety disorders]. 1529 Dec 42

Dysregulation of the hypothalamic-pituitary-adrenocortical axis with deficient glucocorticoid feedback and alterations in the serotonergic system have been identified as biological correlates of mood disorders. Close examination of the interaction between these systems may offer insights into the pathophysiology of anxiety disorders and depression to understand how stress and these disorders are related. In this study, we investigated the relationship between plasma levels of cortisol and the dominant inhibitory serotonergic receptor, serotonin-1A (5-HT1A). Using positron emission tomography (PET) and the radioligand [carbonyl-11C]WAY-100635, we quantified the 5-HT1A receptor binding. Data from 12 male patients with social phobia and 18 matched control subjects were analysed. Seven brain regions were investigated: the anterior and posterior cingulate cortices, hippocampus, amygdala, medial orbitofrontal and retrosplenial cortices, and dorsal raphe nucleus. Partial correlation analysis, controlled for age and radiochemical variables, was performed to demonstrate the association between cortisol plasma levels and 5-HT1A receptor binding. Cortisol plasma levels were significantly lower in patients with social phobia compared to healthy controls. Moreover, we found strong negative correlations between cortisol plasma levels and 5-HT1A binding in the amygdala (r=-0.93, p=0.0004), hippocampus (r=-0.80, p=0.009), and retrosplenial cortex (r=-0.48, p=0.04) in patients with social phobia. Within the former two regions, these associations were significantly higher in patients than in healthy controls. This PET study confirms a negative association between plasma cortisol levels and the 5-HT1A receptor distribution consistent with studies in rodents and non-human primates. Dysregulation of the cortisol level might increase the vulnerability for mood disorders by altering limbic 5-HT1A receptors.
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PMID:Cortisol plasma levels in social anxiety disorder patients correlate with serotonin-1A receptor binding in limbic brain regions. 2051 60