By Bhushan, Vikas
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5). 1) in blocking the voltagesensitive L-type Ca2 + channels in the heart as in the vasculature. 2. First and second generation calcium antagonists A. Drugs which interact with the phenylalkylamine recognition sites in the Ca 2 + channel. Prototype first generation Second generation (X] subunit of the Verapamil Gallopamil Anipamil RO 5967 Falipamil B. Drugs which interact with the dihydropyridine recognition sites in the Ca 2 + channel. Prototype first generation Nifedipine Second generation Amlodipine Felodipine Isradipine Nicardipine Nimodipine Nisoldipine Nitrendipine C.
This interesting aspect of the mode of action of amlodipine is, as is described in the next chapter, an inherent property of the molecule, and hence one which, when coupled with its high bioavailability and slow clearance rate (Chapter 7), sets amlodipine apart from other dihydropyridine based antagonists which are currently in use in Western medicine. Already there are numerous other naturally-long-acting dihydropyridine-based calcium antagonists being developed. The question is, therefore, should there be a third generation of these drugs - with amlodipine as its prototype?
According to this scheme the a subunit consists of two major domains. 3). 3) and two smaller loops connecting the transmembrane helices 2 and 3, and helices 7 and 8. The Na + binding site of the a subunit complex is associated with the amino terminus and the cytoplasmic end of helix 1 whereas the K + and ouabain binding sites are located at or near the ectoplasmic end of helices 2 and 3. ATP binds to the cytoplasmic domain, where it phosphorylates an aspartate residue. The,B subunit of the Na+-K+ pump consists of a single transmembrane spanning helix linking a relatively short aminoterminal domain with a large extracellular globular domain containing glycosylation sites.
Anatomy by Bhushan, Vikas