It is used for preventing angina pectoris. A synonym of this drug is tenormin.
Nadolol: Nadolol is 1-(tert-butylamino)-3-[(5,6,7,8-tetrahydro-c«-6,7-dihydroxy-1-napthyl)-oxy]-2-propanol (12.1.8). The synthesis of this drug is described in Chapter 12.
It is used for preventing chronic angina pectoris. A synonym of this drug is corgard.
These drugs were developed as coronary vasodilating agents and were used for that purpose for some time, until it was discovered that they inhibit the contractile effect of calcium on smooth musculature and cardiac muscle, and that they affect calcium channels on the cell surface that permit calcium ions to enter. At first, they were called calcium antagonists; however, later on this class of compounds was given the preferred name of calcium channel blockers.
Chemically, calcium channel blockers are synthesized up of a fairly diverse group of compounds, which testifies of the diverse receptive regions both on the cell membrane surface as well as within the cell. Verapamil, which can be viewed as a benzylcyanide derivative, is one of the oldest and most actively used compounds of this class up to the present day. Diltiazem is a thiodiazepine, while nifedipin and nicardipine are derivatives of dihy-dropyridine.
It is now obvious that the contraction of smooth muscle is controlled by the concentration of calcium in the cytoplasm. A basic principle of calcium-channel blocker action is that they disturb diffusion of calcium into muscle cells of the heart and vessels. Reduction of calcium ions entering the cells of the myocardium leads to a reduced use of the energy of phosphate bonds for mechanical heart work. As a result, strength of cardiac contractions and heart work are reduced, which in turn leads to a reduction in the heart's need of oxygen.
Two mechanisms of regulating cellular concentrations of calcium have been proposed. The first is called the electromechanical coupling mechanism. It is believed that voltage-gated calcium channels open in response to depolarization of the membrane and in response to extracellular calcium ions rushing into the cell. The second of the proposed mechanisms is not dependent on membrane depolarization. It is believed that calcium ions are released from sarcoplasmic reticulum, which causes an influx of extracellular calcium ions into the cell through open voltage-gated calcium channels. An increased concentration of calcium ions leads to binding with calmodulin. In turn the Ca2+-calmodulin complex initiates phos-phorylation of the myosin light chain by activating light chain kinases. Reaction of phos-phorylated myosin light chains with actin, in turn, causes smooth muscle contraction.
Calcium channel blockers can block the flow of calcium ions into the cell by any of the stated mechanisms. However, voltage-gated channels respond to lower concentrations of Ca2+ than do nonvoltage-gated channels. This implies that the ratio of voltage-gated/nonvoltage-gated channels determines the selectivity of vein and artery responses. In
Was this article helpful?