Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12094
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dc.contributor.authorDillon, J Sen
dc.contributor.authorNayler, W Gen
dc.date.accessioned2015-05-16T01:44:29Z
dc.date.available2015-05-16T01:44:29Z
dc.date.issued1988-05-01en
dc.identifier.citationBritish Journal of Pharmacology; 94(1): 253-63en
dc.identifier.govdoc2456811en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/12094en
dc.description.abstract1. Isolated, Langendorff-perfused rat hearts, isolated membranes, and pharmacological and receptor binding techniques were used to study the properties of the newly developed verapamil derivative, anipamil. 2. When added acutely to isolated, spontaneously beating or electrically paced hearts, anipamil (0.01-0.15 microM) exerted a dose-dependent negative inotropic effect which developed slowly and persisted after 60 min washout. 3. When added acutely (0.05-0.1 microM) to isolated hearts, or when given intravenously (2 mg kg-1 body weight 1 h before the animals were killed), anipamil displaced the dose-response curves for the positive inotropic effect of (0.10-3.0 mM) Ca2+ and (10-50 nM) Bay K 8644 to the right. 4. When added to freshly isolated cardiac membranes, 0.1 microM anipamil increased the dissociation constant (KD) of the phenylalkylamine (-)-[3H]-desmethoxyverapamil ((-)-[3H]-D888) from 1.22 +/- 0.2 to 2.91 +/- 0.46 nM, without any significant change in density (Bmax; control: 163 +/- 17; anipamil: 117 +/- 20 fmol mg-1 protein). Bound (-)-[3H]-D888 was displaceable by (-)-D888 (Ki 1.7 +/- 0.4 nM) greater than (-)-D600 (Ki 12 +/- 0.5 nM) greater than verapamil (Ki 55 +/- 11 nM) greater than (+)-D600 (Ki 108 +/- 12.2) greater than anipamil (Ki 471 +/- 52 nM). 5. In cardiac membranes isolated from rats pretreated with anipamil (2 mg kg-1 i.v.) 1h before they were killed, the KD of (-)-[3H]-D888 binding was increased (P less than 0.05) from 1.59 +/- 0.18 to 3.28 +/-0.65 nM with no significant change in density, compared to the placebo-treated (control) rats. 6. These results establish that anipamil interacts in a competitive manner with the phenylalkylamine binding sites in cardiac membranes, and that it resembles other Ca2+ antagonists in displacing the dose-response curve for the positive inotropic effect of Ca2+ to the right. The results also show that although anipamil binds tightly to the cardiac membranes, it binds to the (-)-[3H]-D888 recognition sites less potently than (-)-D888, (-)-D600 or verapamil.en
dc.language.isoenen
dc.subject.other3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester.pharmacologyen
dc.subject.otherAnimalsen
dc.subject.otherCalcium.pharmacologyen
dc.subject.otherCalcium Channel Blockers.pharmacologyen
dc.subject.otherCalcium Chloride.pharmacologyen
dc.subject.otherElectric Stimulationen
dc.subject.otherHeart Rate.drug effectsen
dc.subject.otherIn Vitro Techniquesen
dc.subject.otherMaleen
dc.subject.otherMyocardial Contraction.drug effectsen
dc.subject.otherPropylamines.pharmacologyen
dc.subject.otherRatsen
dc.subject.otherRats, Inbred Strainsen
dc.subject.otherVerapamil.analogs & derivatives.pharmacologyen
dc.titleThe Ca2+ -antagonist and binding properties of the phenylalkylamine, anipamil.en
dc.typeJournal Articleen
dc.identifier.journaltitleBritish journal of pharmacologyen
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australiaen
dc.description.pages253-63en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/2456811en
dc.type.austinJournal Articleen
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
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