| Link | https://jpet.aspetjournals.org/content/263/2/540 |
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| Author | Search for: Lonsberry, B. B.; Search for: Czubryt, M. P.; Search for: Dubo, D. F.; Search for: Gilchrist, J. S.; Search for: Docherty, J. C.; Search for: Maddaford, T. G.; Search for: Pierce, G. N. |
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| Format | Text, Article |
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| Abstract | The purpose of this study was to determine if chronic administration of verapamil could alter the density of Ca++ channels in the heart as determined by [3H]PN 200-110 binding. Initially, we compared the effects of verapamil given by s.c. injection or via implantable, slow-release verapamil pellets. We found the majority of animals treated with the pellets died within 24 hr. Those that survived exhibited significantly depressed maximal binding and Kd values for PN 200-110 binding to cardiac membranes, but binding to brain membranes was unaffected. Quantitation of the serum levels of verapamil and its metabolites by high-performance liquid chromatography demonstrated that the verapamil pellets did not release the drug evenly over a 3-week period. Most of the drug was released in toxic quantities during the 1st day after implantation. Verapamil administered by injection (2.5-30 mg/kg/day) for up to 16 weeks raised plasma verapamil levels to 25 to 250 ng/ml, but had no effect on Ca++ channel characteristics in cardiac or brain tissue. The maximal binding and Kd values for skeletal muscle PN 200-110 binding were increased only at the highest dosage for 8 weeks duration. Our results demonstrate that implantable pellets are not a reliable administration method for verapamil and cardiac Ca++ channels are highly resistant to change during chronic verapamil administration. |
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| Publication date | 1992 |
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| Publisher | The American Society for Pharmacology and Experimental Therapeutics |
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| In | |
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| Language | English |
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| NRC publication | This is a non-NRC publication"Non-NRC publications" are publications authored by NRC employees prior to their employment by NRC. |
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| NRC number | NRC-IBD-162 |
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| NPARC number | 9147889 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 168d79dc-8192-44a0-94bb-13d2016dac37 |
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| Record created | 2009-06-25 |
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| Record modified | 2023-02-28 |
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