Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clozapine has been found to inhibit the binding of [3H]met-enkephalin to synaptosome-enriched fractions prepared from rat whole brain and hippocampus in a Tris-buffered media without added ions. The IC50 value for hippocampus is 28.5 microM. The inhibition constant for whole brain (41.0 microM) was found to be slightly larger than the corresponding value for chlorpromazine, which was measured under similar experimental conditions.
 ...
PMID:Clozapine inhibition of metenkephalin binding to synaptosome-enriched fractions of rat whole brain and hippocampus. 726 49

The effects of clozapine treatment on neuroendocrine responses induced by the serotonin agonist, m-chlorophenylpiperazine (mCPP) were examined. mCPP and placebo were administered after a 2-week drug-free period and again after 5 weeks of clozapine treatment in nine schizophrenic inpatients. Adrenocorticotropic hormone (ACTH), prolactin, and mCPP levels were measured. Clozapine treatment completely blocked mCPP-induced ACTH and prolactin release suggesting that clozapine blocks serotonin receptors that mediate these hormone responses.
 ...
PMID:Clozapine treatment and its effect on neuroendocrine responses induced by the serotonin agonist, m-chlorophenylpiperazine. 808 Aug 89

Clozapine is an atypical neuroleptic medication with superior efficacy to conventional antipsychotic agents for patients with chronic, symptomatic schizophrenia. Neurochemical characteristics that distinguish clozapine from other neuroleptics and contribute to its differential efficacy are not known. We assessed the effects of clozapine on plasma levels of norepinephrine (NE) in a double-blind, parallel groups comparison of clozapine (n = 11) and haloperidol (n = 15) in chronic schizophrenic outpatients who had been previously treated with fluphenazine. Simultaneous measurements were obtained for plasma levels of the catecholamine precursor dopa, the dopamine metabolite dihydroxyphenylacetic acid (DOPAC), the NE metabolite 3,4-dihydroxyphenylglycol (DHPG), adrenocorticotropin (ACTH), cortisol, and hemodynamic parameters. Clozapine produced marked increases (471%) in plasma NE levels, whereas haloperidol had no significant effects on plasma NE levels. Clozapine also increased dopa and tended to increase DOPAC levels, without effects on DHPG, ACTH, or cortisol levels and without consistent changes in blood pressure. Across patients, the magnitude of clozapine-induced increments in plasma NE levels was positively related to improvement in positive symptoms and global symptomatology and was unrelated to the occurrence of extrapyramidal symptoms. The results suggest that clozapine differs importantly from other neuroleptics in increasing plasma NE levels, with the peripheral noradrenergic stimulation related to its superior efficacy profile. The unchanged DHPG levels and absence of hypertension suggest a more complex mechanism of action of clozapine than heightened NE release alone.
 ...
PMID:The effect of clozapine on plasma norepinephrine: relationship to clinical efficacy. 817 90

Antipsychotic drugs can regulate transcription of some genes, including those involved in regulation of hypothalamic-pituitary-adrenal (HPA) axis, whose activity is frequently disturbed in schizophrenic patients. However, molecular mechanism of antipsychotic drug action on the corticotropin-releasing hormone (CRH) gene activity has not been investigated so far. This study was undertaken to examine the influence of conventional and atypical antipsychotic drugs on the CRH gene promoter activity in differentiated Neuro-2A cell cultures stably transfected with a human CRH promoter fragment linked to the chloramphenicol acetyltransferase (CAT) reporter gene. It has been found that chlorpromazine (0.1-5.0 microM), haloperidol (0.5-5.0 microM), clozapine (1.0-5.0 microM), thioridazine (1.0-5.0 microM), promazine (5.0 and 10 microM), risperidone (5.0 and 10.0 microM), and raclopride (only at the highest used concentrations, ie 30 and 100 microM) present in culture medium for 5 days inhibited the CRH-CAT activity. Sulpiride and remoxipride had no effect. Since CRH gene activity is most potently enhanced by cAMP/protein kinase A pathway, the effect of antipsychotics on the forskolin-induced CRH-CAT activity was determined. Chlorpromazine (1.0-5.0 microM), haloperidol (1.0-5.0 microM), clozapine (1.0-5.0 microM), thioridazine (3.0 and 5.0 microM), and raclopride (30 and 100 microM), but not promazine, sulpiride, risperidone, and remoxipride, inhibited the forskolin-stimulated CRH gene promoter activity. A possible involvement of protein kinases in chlorpromazine and clozapine inhibitory action on CRH activity was also investigated. It was found that wortmannin (0.01 and 0.02 microM), an inhibitor of phosphatidylinositol 3-kinase (PI3-K), significantly attenuated the inhibitory effect of chlorpromazine and clozapine on CRH gene promoter activity. In line with these results, a Western blot study showed that these drugs increased phospho-Ser-473 Akt level, had no effect on total Akt, and decreased glycogen synthase kinase-3beta level. Additionally, we found that clozapine decreased protein kinase C (PKC) level and that its action on CRH activity was attenuated by PKC activator (TPA, 0.1 microM). The obtained results indicate that inhibition of CRH gene promoter activity by some antipsychotic drugs may be a molecular mechanism responsible for their inhibitory action on HPA axis activity. Clozapine and chlorpromazine action on CRH activity operates mainly through activation of the PI3-K/Akt pathway. Moreover, PKC-mediated pathway seems to be involved in clozapine action on CRH gene activity.
 ...
PMID:Antipsychotic drugs inhibit the human corticotropin-releasing-hormone gene promoter activity in neuro-2A cells-an involvement of protein kinases. 1620 82