Drugs online research references
Biochem Pharmacol. 1991 Oct 24;42(10):1875-8.
Effects of the enantiomers of lansoprazole (AG-1749) on (H+ + K+)-ATPase activity in canine gastric microsomes and acid formation in isolated canine parietal cells.
Nagaya H, Inatomi N, Nohara A, Satoh H.
Biology Research Laboratories, Takeda Chemical Industries Ltd, Osaka, Japan.
The effects of the enantiomers of 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]-sulfinyl ]- 1H-benzimidazole (lansoprazole, AG-1749) on acid formation in isolated canine parietal cells and (H+ + K+)-ATPase activity in canine gastric microsomes were investigated. Both the (+)-and the (-)-enantiomer of lansoprazole inhibited the acid formation stimulated by dibutyryl cyclic AMP (db-cAMP) in isolated canine parietal cells in a concentration-dependent manner with IC50 values of 59 and 82 nM, respectively. The enantiomers showed concentration-dependent inhibition of (H+ + K+)-ATPase with IC50 values of 4.2 and 5.2 microM, respectively. On the other hand, the IC50 values of lansoprazole for db-cAMP-stimulated acid formation and (H+ + K+)-ATPase were 59 nM and 2.1 microM, respectively. These results suggest that the two enantiomers of lansoprazole have antisecretory action due to inhibition of (H+ + K+)-ATPase.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1660270&dopt=Abstract
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Am J Physiol. 1991 Aug;261(2 Pt 1):G206-12.
Electrical characteristics of inward-rectifying K+ channels in isolated bullfrog oxyntic cells.
Mieno H, Kajiyama G.
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
The properties of K+ channels in the isolated oxyntic cells of the bullfrog (Rana catesbeiana) were investigated using the patch-clamp method. Two types of K+ channels on the basolateral membrane were identified on the basis of their electrophysiological and pharmacological properties. The K+ channel most frequently observed has a single-channel conductance of 61.0 +/- 2.9 pS (n = 10) and is activated by an increase in intracellular Ca2+. The other K+ channel has a single-channel conductance of 30.3 +/- 2.7 pS (n = 7), which is activated by adenosine 3',5'-cyclic monophosphate (cAMP). The physiological and pharmacological characteristics common to the two K+ channels are inward-going rectification with a high selectivity for K+ and indirect inhibition by omeprazole. The inward rectification is controlled by intracellular Mg2+ in such a way that the more Mg2+ is applied intracellularly, the more their inward-rectifying property is enhanced. The finding that bethanechol and cAMP increase the open probability of these K+ channels as well as activating the acid secretion indicates that there may be a relationship between these two processes in the oxyntic cells.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1678585&dopt=Abstract
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Mutagenesis. 1991 Sep;6(5):381-4.
Omeprazole: an exploration of its reported genotoxicity.
Rosenkranz HS, Klopman G.
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, PA 15261.
Because of its reported ability to induce unscheduled DNA synthesis in the gastric mucosa, the safety of omeprazole, a potentially clinically useful anti-ulcer drug, has been the subject of debate. We have undertaken a detailed computer-based study of structural basis of the putative mutagenicity, genotoxicity and carcinogenicity in rodents of omeprazole and of its sulphenimide, and we conclude that omeprazole is a potential 'genotoxic' carcinogen. The analysis is consistent with the possibility that these activities are associated with the unstable sulphenimide metabolite.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1795642&dopt=Abstract
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