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)

To determine if the mechanism of action of clinical and investigational antiepileptic and antimyoclonic drugs or neuropeptides involves direct actions at serotonin (5-HT) receptors, the activity of various compounds in vitro at 5-HT1 (with subtypes) and 5-HT2 sites was measured in adult rat brainstem, spinal cord, and neocortex. Adrenocorticotropic hormone (ACTH1-39) noncompetitively inhibited specific binding at 5-HT1, 5-HT1A, and 5-HT2 sites in brainstem and neocortex [concentrations required to displace 50% of ligand binding (IC50S) 4-8 X 10(-5) M]. ACTH1-24, ACTH1-17, and ACTH4-10 were sequentially less active, and ACTH34-39 and corticosterone were inactive. D-Ala2, Leu5-enkephalinamide, but not D-Ala2, Met5-enkephalinamide, also displaced spinal and neocortical 5-HT2 sites (IC50 6 X 10(-5) M). Piracetam, glycine, and the clinical antiepileptics valproate, phenacemide, phenytoin, carbamazepine, phenobarbital, diazepam, clonazepam, nitrazepam, and ethosuximide did not displace serotonergic radioligands, but melacimide showed some activity at 5-HT1 sites (IC50 7-9 X 10(-5) M). Anticonvulsant inactivity at 5-HT receptors in vitro correlates with the lack of antimyoclonic activity in 5-HT lesion myoclonic models but not with antimyoclonic efficacy in humans. These data indicate that acute effects of these anticonvulsants cannot be attributed to direct action at the 5-HT receptor recognition site in the rat. In contrast, ACTH showed mild in vitro displacement and regional specificity but only at micromolar concentrations.
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PMID:Effect of antiepileptic and antimyoclonic drugs on serotonin receptors in vitro. 283 32