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)

Auditory evoked middle latency responses recorded in the hippocampus (HAER), were monitored in alert, gently restrained rats with chronic indwelling electrodes and cannulae. Intrahippocampal (i.h.) injection of 5-hydroxytryptamine (5-HT, 10 micrograms) reduced the amplitude and increased the latency of the N28 and P55 peaks of the HAER. An early (P18) negative peak was unaffected. Buspirone (1 microgram, i.h. and 3 mg/kg, i.p.) had similar effects to those produced by i.h. 5-HT. RU 24969 (1 mg/kg, s.c.) also reduced the amplitude of the N28 peak of the HAER. Long-term treatment with buspirone for 14 days at a dose (0.5 mg/kg, i.p.) which when applied acutely did not produce any observable effect, caused an increase in the latency of both the N28 and P55 peaks. Direct i.h. injection of 5-HT into these chronically treated animals did not have any additional depressant effect on the HAER peaks. It is concluded that these serotoninergic agonists can modulate the later peaks of the HAER possibly via 5-HT1A receptors. In the case of buspirone there was evidence of an enhanced depressant effect following chronic treatment [corrected].
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PMID:Serotoninergic depression of auditory evoked responses recorded in the rat hippocampus: effect of repeated buspirone treatment. 150 59

In the present study experimentally determined ligand selectivity of three methylated buspirone analogues (denoted as MM2, MM5 and P55) towards 5-HT1A and 5-HT2A serotonin receptors was theoretically investigated on a molecular level. The relationships between the ligand structure and 5-HT1A and 5-HT2A receptor affinities were studied and the results were found to be in agreement with the available site-directed mutagenesis and binding affinity data. Molecular dynamics (MD) simulations of ligand-receptor complexes were performed for each investigated analogue, docked twice into the central cavity of 5-HT1A/5-HT2A, each time in a different orientation. Present results were compared with our previous theoretical results, obtained for buspirone and its non-methylated analogues. It was found that due to the presence of the methyl group in the piperazine ring the ligand position alters and the structure of the ligand-receptor complex is modified. Further, the positions of derivatives with pyrimidinyl aromatic moiety and quinolinyl moiety are significantly different at the 5-HT2A receptor. Thus, methylation of such derivatives alters the 3D structures of ligand-receptor complexes in different ways. The ligand-induced changes of the receptor structures were also analysed. The obtained results suggest, that helical domains of both receptors have different dynamical behaviour. Moreover, both location and topography of putative binding sites for buspirone analogues are different at 5-HT1A and 5-HT2A receptors.
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PMID:Molecular dynamics of 5-HT1A and 5-HT2A serotonin receptors with methylated buspirone analogues. 1198 22