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 effects of postmortem delay, time of storage, and freezing, thawing, and refreezing tissue samples were studied in postmortem rat brain using conditions that reflect the handling of postmortem human brain before neurochemical analysis. The levels of monoamines and metabolites in the striatum and cingulate and occipital cortex were measured using alumina extraction and HPLC methods. Binding of raclopride to dopamine D2, SCH-23390 to dopamine D1, ketanserin to serotonin 5-HT2, 8-hydroxy-2-(di-n-propylamino)tetralin to serotonin 5-HT1A, and cholecystokinin (CCK)-8 to CCK-B sites was measured in tissue homogenates from the striatum or fronto-parietal cortex. An 18-h postmortem delay before dissection and storage resulted in region-specific changes in monoamine and metabolite levels. Binding to striatal D1 and frontoparietal cortex CCK-B sites was reduced over the course of a 27-h postmortem delay. Binding to D2 and 5-HT sites was relatively stable. Storage of tissue for up to 8 months also resulted in region-specific changes in monoamine and metabolite levels. No changes in receptor binding were seen after long-term storage. Freezing, thawing, and refreezing tissue samples resulted in increased levels of striatal 3,4-dihydroxyphenylacetic acid and decreased binding to striatal D2 sites. These results demonstrate time-, temperature-, and storage-dependent regional differences in the stability of monoamines and their metabolites and in binding to various receptor sites. These differences in stability and binding should be accounted for to interpret accurately the effects of neurological disorders on neurotransmitter dynamics in postmortem human brain tissue.
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PMID:Postmortem stability of monoamines, their metabolites, and receptor binding in rat brain regions. 750 13

Benzodiazepines (BDZ), the most popular drug of choice for treating anxiety disorders, present side-effects such as sedation, muscular disorders, abuse liability and synergistic effect with alcohol and CNS depressant drugs. At present, pharmacological research is focusing to find anxiolytic drugs as efficacious as benzodiazepines but without side-effects. This review reports the status of the pharmaceutical research and development on novel drugs for the treatment of anxiety disorders. A close analysis of the items selected by the N5C "Pharmaprojects" search (anxiolytic class) yielded the following classification: A) Drugs interacting with the GABA-A receptor complex, which includes BDZ-like drugs, partial BDZ agonists (beta-carbolines) and drugs interacting with the GABA-A complex through an as yet unidentified mechanism (15 compounds), B) Drugs acting as CCK-B antagonists (5 compounds), C) Drugs interacting with serotonergic function (30 compounds) subdivided into: (i) agonists at the 5-HT1A receptor, (ii) antagonists at the 5-HT2 receptor, and (iii) antagonists at the 5-HT3 receptor; D) Drugs with other mechanisms (22 compounds). Based on these results, it is not possible to identify a common mechanism through which the selected drugs under development exert their anxiolytic effect. Therefore, it appears that different biological mechanisms are specifically involved in the different anxiety disorders.
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PMID:New anxiolytics in development. 791 35

Presently available clinical genetic studies point to a considerable heritability of anxiety disorders (30-67%), with multiple vulnerability genes such as 5-HT1A, 5-HTT, MAO-A, COMT, CCK-B, ADORA2A, CRHR1, FKBP5, ACE, RGS2/7 and NPSR1 suggested by molecular genetic association studies. These genes have been shown to partially interact with each other as well as with environmental factors to shape the overall disease risk in a complex genetic model. Additionally, recent studies have pointed out the crucial role of epigenetic signatures such as methylation patterns in modifying environmental influences as well as in driving the functional impact of anxiety disorder risk genes. On a systems level, vulnerability genes of anxiety disorders seem to confer some of the disease risk via intermediate phenotypes like behavioral inhibition, anxiety sensitivity or several neurobiological traits such as increased startle reactivity or dysfunctional corticolimbic activity during emotional processing. Finally, first pharmaco- and psychotherapy-genetic studies provide evidence for certain risk genes to confer interindividual variability in response to a pharmacological or psychotherapeutic intervention in anxiety disorders. Genetic research in anxiety disorders will be discussed regarding its potential to foster innovative and individually tailored therapeutic approaches for patients with anxiety disorders.
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PMID:Genetic factors in anxiety disorders. 2522 16