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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hughes, A. D. Wijetunge, S. |
| Description | Author Affiliation: Hughes AD ( Department of Clinical Pharmacology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London.) |
| Abstract | 1. Amlodipine, a dihydropyridine derivative largely ionized at physiological pH, inhibited calcium channel currents in single vascular smooth muscle cells isolated from rabbit ear artery in a concentration-dependent manner. 2. Amlodipine inhibited the current-voltage relationship for calcium channel currents across the range of test potentials used. However, the effect of amlodipine was more marked on more depolarized test potentials. Amlodipine also shifted the steady-state inactivation curve for calcium channel currents in a hyperpolarized direction. 3. The potency of amlodipine as determined from the steady-state inhibition of calcium channel current induced by the drug was dependent on the holding potential of the cells. Use of a more depolarized holding potential increased the potency of amlodipine. 4. Onset of amlodipine-induced inhibition was relatively rapid at both -60 mV and -40 mV holding potential. The use of a more depolarized holding potential increased the rate of association of amlodipine. No recovery from amlodipine-induced inhibition was seen over a 20 min period following washout of the drug. 5. In addition to voltage-dependence, the action of amlodipine showed use-dependence, in that the effect of amlodipine was more marked when calcium channel currents were evoked frequently. Increasing the frequency of activation of calcium channel currents did not alter the apparent onset rate of amlodipine-induced inhibition, but increased the degree of inhibition achieved by the drug. 6. The electrophysiological properties of amlodipine, particularly its voltage-dependence are probably important determinants of its action in vivo. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 109 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1993-05-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Amlodipine Pharmacology Calcium Channels Drug Effects Muscle, Smooth, Vascular Metabolism Animals Electrophysiology Hydrogen-Ion Concentration In Vitro Techniques Rabbits Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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