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)

We built a model for the 5-HT1A receptor, using the 3D-structure of bacteriorhodopsin as a structural template. With the use of site-directed mutagenesis data, several potent 5-HT1A agonists, belonging to five different structural classes, and an aryloxypropanolamine antagonist, were docked into the receptor model. After docking, the surrounding of the ligands appeared to be in full agreement with previously reported SAR-data of 5-HT1A ligands. In this study, for the first time, an explanation for 5-HT SAR results is given in terms of interactions between ligands and amino acid residues. Also the selectivity of 8-OH-DPAT for the 5-HT1A receptor is accounted for. In our model the agonists and the antagonist interact with different residues on several helices. They all interact with the essential aspartic acid on helix III, that is known to bind all amines to receptors for biogenic amines. This partial overlap of the binding sites accounts for the antagonism of the class of aryloxypropanolamines and for the deviating SAR of this class of compounds when compared to agonists.
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PMID:A model of the serotonin 5-HT1A receptor: agonist and antagonist binding sites. 754 38

Ketamine, a dissociative anesthetic agent, appears to have rapid antidepressant effects at sub-anesthetic doses in clinically depressed patients. Although promising, these results need to be replicated in double-blind placebo-controlled studies, a strategy thwarted by the psychoactive effects of ketamine, which are obvious to both patients and clinicians. Alternatively, demonstrations of the psychotherapeutic effects of ketamine in animal models are also complicated by ketamine's side-effects on general activity, which have not been routinely measured or taken into account in experimental studies. In this study we found that ketamine decreased "behavioral despair" in the forced swim test, a widely used rats model of antidepressant drug action. This effect was not confounded by side-effects on general activity, and was comparable to that of a standard antidepressant drug, fluoxetine. Interestingly, ketamine also produced anxiolytic-like effects in the elevated-plus-maze. Importantly, the effective dose of ketamine in the plus-maze did not affect general locomotion measures, in either the plus-maze or in the open field test. While the selective N-methyl-d-aspartic acid (NMDA) receptor antagonist MK-801 also produced antidepressant-like and anxiolytic-like effects, these were mostly confounded by changes in general activity. Finally, in a neurophysiological model of anxiolytic drug action, ketamine reduced the frequency of reticularly-activated theta oscillations in the hippocampus, similar to the proven anxiolytic drug diazepam. This particular neurophysiological signature is common to all known classes of anxiolytic drugs (i.e. benzodiazepines, 5-HT1A agonists, antidepressants) and provides strong converging evidence for the anxiolytic-like effects of ketamine. Further studies are needed to understand the underlying pharmacological mechanisms of ketamine's effects in these experiments, since it is not clear they were mimicked by the selective NMDA antagonist MK-801.
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PMID:Anxiolytic- and antidepressant-like properties of ketamine in behavioral and neurophysiological animal models. 1932 Nov 51