Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12094
Title: The Ca2+ -antagonist and binding properties of the phenylalkylamine, anipamil.
Authors: Dillon, J S;Nayler, W G
Affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Issue Date: 1-May-1988
Citation: British Journal of Pharmacology; 94(1): 253-63
Abstract: 1. 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.
Internal ID Number: 2456811
URI: http://ahro.austin.org.au/austinjspui/handle/1/12094
URL: http://www.ncbi.nlm.nih.gov/pubmed/2456811
Type: Journal Article
Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester.pharmacology
Animals
Calcium.pharmacology
Calcium Channel Blockers.pharmacology
Calcium Chloride.pharmacology
Electric Stimulation
Heart Rate.drug effects
In Vitro Techniques
Male
Myocardial Contraction.drug effects
Propylamines.pharmacology
Rats
Rats, Inbred Strains
Verapamil.analogs & derivatives.pharmacology
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.