Biomedical Engineering Reference
In-Depth Information
effect on coronary resistance resulting in coronary steal in the presence of
hypoperfused regions. It may also be caused by the reactive sympathetic activation
with increase in heart rate and cardiac oxygen consumption.
Epidemiological and case-control studies suggested that Ca
2
þ
channel blockers
cause increased risk for myocardial infarction, cancer and gastrointestinal bleeding.
The increased cardiovascular morbidity was again associated with short-acting
dihydropyridines and fast release forms of verapamil and diltiazem.
3 Conclusion
Calcium channel blockers inhibit calcium uptake, block smooth muscle contraction
and bind to the receptor sites associated with the voltage-dependent calcium ion
channels. All these activities have been found to be mutually correlated [
109
].
Different linear and nonlinear methods have been used in QSAR studies to obtain
additional and more precise physicochemical parameters that are important for the
biological activity of calcium ion channel blockers and for the design of more
selective molecules [
110
].
Even today, the studies on the calcium channel blockers remained centered
around the dihydropyridines. QSAR studies of 4-phenyl-substituted dihydro-
pyridines indicate unfavorable steric interactions for bulky moieties in the
para-
position of the phenyl ring and that bulky substituents are favorable in
ortho
- and
meta
-positions. The best combination is obtained when the bulky substituents
at
ortho
-or
meta-
positions produce negatively charged electrostatic potential.
Further, investigation and studies are still needed to delineate the physicochemical
parameters implicated in the case of the nondihydropyridines.
References
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Dev Res 42:131-143
2. Catterall WA (1994) Molecular properties of a superfamily of plasma-membrane cation
channels. Curr Opin Cell Biol 6:607-615
3. Walker D, De Waard M (1998) Subunit interaction sites in voltage-dependent Ca
2
þ
channels: role in channel function. Trends Neurosci 21(4):148-154
4. Fatt P, Katz B (1953) The electrical properties of crustacean muscle fibres. J Physiol
120:171-204
5. Fatt P, Ginsborg BL (1958) The ionic requirements for the production of action potentials in
crustacean muscle fibres. J Physiol 142:516-543
6. Hagiwara S, Byerly L (1981) Calcium channel. Annu Rev Neurosci 4:69-125
7. Dolphin AC (2006) A short history of voltage-gated calcium channels. Br J Pharmacol
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