Download Calcium Channel Pharmacology by Evgeni N. Timin, Stanislav Berjukow, Steffen Hering (auth.), PDF

By Evgeni N. Timin, Stanislav Berjukow, Steffen Hering (auth.), Stefan I. McDonough (eds.)

Voltage-gated calcium channels are severe regulators of cytoplasmic degrees of calcium, the common signaling ion. As such, calcium channels set off quite a lot of mobile features, from muscle contraction to neurotransmitter secretion, and are very important gamers in human illness. fashionable within the fearful, cardiovascular, and endocrine structures, individuals of the calcium channel kinfolk are objectives for latest antihypertensive and anticonvulsant medicines. moreover, they're rising ambitions for medications to regard a very different workforce of issues, together with discomfort, cerebral ischemia, cardiac arrhythmia, and migraine. This publication stories the compounds that focus on person calcium channel subtypes and the mobile and behavioral services ruled by way of each one diverse channel. It comprises details for simple scientists utilizing calcium channel antagonists as experimental instruments, for behavioralists learning animal types of human illness, and for pharmaceutical scientists drawn to growing the following iteration of calcium channel-targeted medicines. a number of elements make a whole e-book on calcium channel pharmacology timely.

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Example text

2. , 1997; Striessnig et at, 1998). , 1997). , 1997). These "reconstructed" channels possess the principal characteristics of 1,4dihydropyridine activator and antagonist properties, stereoselectivity, and voltagedependence of action. 2 channels. The location of these critical residues on illS5, illS6, and IVS6 is consistent with a domain model in which the binding site for I,4-dihydropyridines is located at the interface of domains . ill and IV (Catterall and Striessnig, IV III 1992; Lipkind and Fozzard, 2(03).

This selectivity of action is a major determinant of the observed pharmacological and therapeutic selectivity of action observedfor the agents depictedin Figures 2 and 3. It is worthyof observation that thus far it is only the Cavl subclass of calciumchannelthat has yielded small molecule therapeutically active agents: the other channel classes are well defined by potent and selective toxins that are a prominent part of Nature's armamentarium, but despite considerable effort have not yieldedto the more useful small molecule agents.

1992). , 1989). These activators oJ"AMe COOH Me interact at a site partially distinct from the CGP4I5OI 1,4-dihydropyridine site and linked in Figure 8. L-type llIonists. , calcium channels. 1991). , 2000 ; Kunze and Rampe, 1992). , 1995; Herzig, 1996). , 1986). o O=CtrCOOMe x~ ~'N~ V-[).. 4. Peptide Toxins The L-type calcium channel was the first (and best) characterized pharmacologically and has been characterized largely by small molecule synthetic ligands, in contrast to the neuronal N-type , P/Q-type (and some R-type) channels that are still characterized almost exclusively by peptide toxins.

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