Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of viral respiratory infection by Sendai virus on bronchial responses to aerosolized histamine in anesthetized guinea pigs and on the activity of histamine N-methyltransferase (HMT). We measured the change in total pulmonary resistance induced by histamine in the presence or absence of a specific HMT inhibitor, SKF 91488, in noninfected and infected animals. In the absence of SKF 91488, the bronchoconstrictor response to histamine was greater in infected than in noninfected animals. SKF 91488 (10(-2) M, 90 breaths) potentiated the responses to histamine in noninfected animals, and the magnitude of augmented responses to histamine by SKF 91488 was similar to that by viral infection. Furthermore, SKF 91488 did not further potentiate the responses to histamine in infected animals. However, responses to aerosolized acetylcholine were unaffected by viral infection and SKF 91488. The HMT activity decreased by 56% in the trachea, 86% in the bronchi, and 52% in the parenchymal tissue in the infected animals. In contrast to HMT activity, acetylcholinesterase activity was unaffected by viral infection. These results suggest that respiratory infection by Sendai virus causes enhanced bronchial responsiveness to histamine by decreasing HMT activity in airways.
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PMID:Viral respiratory infection causes airway hyperresponsiveness and decreases histamine N-methyltransferase activity in guinea pigs. 817 57

Following tacrine administration i.p. to mice, the histamine N-methyltransferase activity of brain homogenates was more potently inhibited than the acetylcholinesterase activity (ID50 of 5.3 mg/kg vs. 13.6 mg/kg). The formation of the metabolite, tele-methylhistamine, in brain of mice treated with an histamine H3 receptor antagonist was abolished by tacrine with an ID50 as low as 1.2 +/- 0.4 mg/kg. The participation of histamine in the actions of tacrine and the relevance of histamine H3 receptor antagonists in Alzheimer's disease are suggested.
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PMID:Inhibition of histamine versus acetylcholine metabolism as a mechanism of tacrine activity. 896 Aug 73

Recently developed multi-targeted ligands are novel drug candidates able to interact with monoamine oxidase A and B; acetylcholinesterase and butyrylcholinesterase; or with histamine N-methyltransferase and histamine H3-receptor (H3R). These proteins are drug targets in the treatment of depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease. A probabilistic method, the Parzen-Rosenblatt window approach, was used to build a "predictor" model using data collected from the ChEMBL database. The model can be used to predict both the primary pharmaceutical target and off-targets of a compound based on its structure. Molecular structures were represented based on the circular fingerprint methodology. The same approach was used to build a "predictor" model from the DrugBank dataset to determine the main pharmacological groups of the compound. The study of off-target interactions is now recognised as crucial to the understanding of both drug action and toxicology. Primary pharmaceutical targets and off-targets for the novel multi-target ligands were examined by use of the developed cheminformatic method. Several multi-target ligands were selected for further study, as compounds with possible additional beneficial pharmacological activities. The cheminformatic targets identifications were in agreement with four 3D-QSAR (H3R/D1R/D2R/5-HT2aR) models and by in vitro assays for serotonin 5-HT1a and 5-HT2a receptor binding of the most promising ligand (71/MBA-VEG8).
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PMID:Predicting targets of compounds against neurological diseases using cheminformatic methodology. 2542 29