1. Antiarrythmics, regulating the timing of heart muscle contraction and thus being
useful in the treatment of heart rhythm irregularities which cause palpitations
2. Hypotensives, relaxing heart muscle and being used to treat high blood pressure
3. Anti-anginal agents, counteracting the chest pain of atherosclerotic coronary artery
ischemia
4. Vasoactive agents, for disorders such as migraine headache, Raynaud’s syndrome
(vasospasm of peripheral vessels, producing cold, blue fingers), and Prinzmetal
angina (vasospasm of large, surface coronary arteries in the heart, distinct and
separate from the atherosclerotic angina described above)
As evidenced by this list, the treatment of cardiovascular diseases by Ca
2+ channel
antagonists is the most important. The contraction of cardiac muscle is based on the
interaction of the proteins actin and myosin, which converts the energy of ATP into
mechanical work. ATP hydrolysis is mediated by the enzyme adenosine triphosphatase
(ATPase), which requires the binding of Ca
2+ ions to regulatory proteins, the tropomyosin–
troponin complex. When Ca
2+ is pumped out of the cytosol, contraction ceases and the
muscle relaxes. The cardiac troponin complex is a substrate for a cAMP-dependent protein kinase, leading to desensitization that counteracts catecholaminergic stimulation.
The uptake of Ca
2+ from the cytosol into the sarcoplasmic reticulum of cardiac muscle
is regulated by an ATP-dependent Ca
2+ pump, which allows for Ca pooling until Ca
2+
ions are needed again. During the excitation–contraction coupling of heart muscle there
is a fast influx of Na
+ ions, causing a rapid action potential, and a slow influx of Ca
2+
,
causing a plateau phase of the action potential. The slow Ca
2+ channel causes depolarization and a rise in Ca
2+ concentration, and triggers Ca
2+ release from the endoplasmic
reticulum. In addition, there is also a 3 Na
+
: 1 Ca
2+ port–antiport system, which moves
426
MEDICINAL CHEMISTRY
useful in the treatment of heart rhythm irregularities which cause palpitations
2. Hypotensives, relaxing heart muscle and being used to treat high blood pressure
3. Anti-anginal agents, counteracting the chest pain of atherosclerotic coronary artery
ischemia
4. Vasoactive agents, for disorders such as migraine headache, Raynaud’s syndrome
(vasospasm of peripheral vessels, producing cold, blue fingers), and Prinzmetal
angina (vasospasm of large, surface coronary arteries in the heart, distinct and
separate from the atherosclerotic angina described above)
As evidenced by this list, the treatment of cardiovascular diseases by Ca
2+ channel
antagonists is the most important. The contraction of cardiac muscle is based on the
interaction of the proteins actin and myosin, which converts the energy of ATP into
mechanical work. ATP hydrolysis is mediated by the enzyme adenosine triphosphatase
(ATPase), which requires the binding of Ca
2+ ions to regulatory proteins, the tropomyosin–
troponin complex. When Ca
2+ is pumped out of the cytosol, contraction ceases and the
muscle relaxes. The cardiac troponin complex is a substrate for a cAMP-dependent protein kinase, leading to desensitization that counteracts catecholaminergic stimulation.
The uptake of Ca
2+ from the cytosol into the sarcoplasmic reticulum of cardiac muscle
is regulated by an ATP-dependent Ca
2+ pump, which allows for Ca pooling until Ca
2+
ions are needed again. During the excitation–contraction coupling of heart muscle there
is a fast influx of Na
+ ions, causing a rapid action potential, and a slow influx of Ca
2+
,
causing a plateau phase of the action potential. The slow Ca
2+ channel causes depolarization and a rise in Ca
2+ concentration, and triggers Ca
2+ release from the endoplasmic
reticulum. In addition, there is also a 3 Na
+
: 1 Ca
2+ port–antiport system, which moves
426
MEDICINAL CHEMISTRY