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)

Several clinical and experimental findings suggest that abnormal serotonin (5-HT) function may be involved in movement disorders such as dystonia, and it was proposed that selective 5-HT1A receptor antagonists may be of benefit in treating such disorders. In the present study, the novel, highly selective and silent 5-HT1A receptor antagonist (+)-WAY-100135 (N-tert-butyl-3(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylprop ionamide) was tested in an inbred line of Syrian hamsters with generalized dystonia, i.e. a frequent movement disorder in humans. In order to demonstrate that WAY-100135 acts as a 5-HT1A receptor antagonist in the hamster, the drug was shown to antagonize the behavioural syndrome induced by 8-hydroxy-2-(di-n-propylamino)tetralin. When administered at 5-HT1A receptor antagonistic doses in dystonic hamsters, (+)-WAY-100135 dramatically aggravated the dystonic attacks. The data thus suggest that, in contrast to previous theoretical proposals, 5-HT1A receptor antagonists provide no novel therapeutic approach to involuntary movement disorders such as dystonia.
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PMID:The novel selective and silent 5-HT1A receptor antagonist (+)-WAY-100135 aggravates dystonic movements in a mutant hamster model. 802 48

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are second only to Alzheimer's disease (AD) in frequency. In particular it is evident that up to 80% of people with PD will develop dementia towards the end of their life. While the neurobiology of movement disorder has been well studied in PD, much less attention has been given to mechanisms underlying the cognitive and behavioural symptoms associated with DLB and PDD. To date, the best correlate of cognitive impairment appears to be cortical Lewy bodies; however, new emphasis has been placed on small aggregates of synuclein. Furthermore, very few studies have attempted to investigate the neurochemical correlates of behavioural disorders in DLB/PDD and whether these are similar or distinct from AD. Aggregated alpha-synuclein forms the core component of Lewy bodies, a major pathological feature of Parkinson's-related conditions. The 26S proteasome is an ATP-dependent protease that catalyses the breakdown of alpha-synuclein. Previous studies have implicated alterations in the proteasome in PD. Furthermore, proteasome inhibitors have been reported to induce alpha-synuclein aggregation and Lewy body-like inclusions, resulting in neuronal loss both in vitro and in vivo. Our preliminary results indicate that selective alterations in the expression of proteosome sub-units are a feature of both DLB and PDD, while changes in activity are restricted to PDD. Depression is a common symptom in DLB/PDD, yet the evidence base for standard treatment with SSRIs is limited. In contrast to previous studies of AD, our results indicate that there is no association between depression and the 5-HT transporter, while there was a significant increase in the number of 5-HT1A receptors in those DLB/PDD patients with depression. These data may provide an insight into the lack of success of current treatments and suggest alternative approaches.
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PMID:Biochemical and pathological correlates of cognitive and behavioural change in DLB/PDD. 1971 Nov 17

The objective of this study is to establish which subdivision of the dorsal raphe nucleus (DRN) supplies serotonergic projections to the subthalamic nucleus (STN) in the rat brain. Several studies in recent years have shown that serotonin (5-HT) might have a therapeutic role in the most prevalent basal ganglia (BG) movement disorder, Parkinson's disease (PD), but, because of the depletion of dopaminergic input to the BG, l-DOPA has been the main treatment for PD patients. Autoradiography showed that serotonin receptors 5-HT1B and 5-HT2C and the serotonin transporter were present in STN, whereas the 5-HT1A and 5-HT2A not were present. Retrograde tracer FluoroGold or Choleratoxin subunit B were iontophoretically delivered in the STN and combined with immunohistochemistry for 5-HT in order to map the topographic organization in the dorsal raphe system. The study showed that approximately 320+/-137 neurons were retrogradely traced from each STN to the DRN, located mainly in the dorsal- and ventrolateral DRN, and of these 108+/-42 or 34% co-localized 5-HT. Additionally anterograde tracer PHA-L was injected in the DRN to confirm projections to STN and accordingly only a sparse number of axon terminals were observed in the STN.
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PMID:Serotonergic projections from the raphe nuclei to the subthalamic nucleus; a retrograde- and anterograde neuronal tracing study. 2668 5