- 期刊
- OpenAccess
鈣離子通道阻斷劑：改善腦循環及增強記憶力之藥效評估
Calcium Channel Blockers: An Evaluation of Their Effects on Improving Cerebral Circulation and Memory Enhancement
摘要
鈣離子幾乎是所有細胞生理功能之重要調節者，而為了執行其生理功能，鈣離子之移動可來自細胞貯存所，或由細胞外進入細胞，在細胞沒有興奮時，細胞內游離鈣離子濃度僅有0.1μM，比細胞外濃度低一萬倍。鈣離子可由“快＂或“慢＂通道進入細胞。“快＂通道即是由接受器控制之通道，主要是由細胞表面接受器與配位體（即神經傳遁物質、荷爾蒙或藥物）結合所形成之複合體活化。生物體內，甚至細胞內，均具有複雜之調節系統來監督正常生理狀況之鈣離子平衡。但在許多病理狀況，進九細胞鈣離子之量失控，破壞了細胞內外之濃度差，細胞可能因此無法存活或失去活性。而此現象之累積發展終將造成各種不同之病理反應。近年來所發展出之“鈣離子通道阻斷劑＂，即是減少鈣離子進入細胞內，因而減少這些病理反應，它們主要作用於由電位控制之通道，而此類通道至少有三型：短暫（T型），長效（L型）及神經（N型）三型，而且各種鈣離子通道阻斷劑對各型之鈣離子通道之作用亦不盡相同。最近之實驗證據更顯示：在不同之帝國截具有不同形式的鈣離子通道蛋白，而且鈣離子阻斷劑之化學結構及最大藥效亦不盡相同，而使得此類藥物之藥理複雜。本文僅就鈣離子通道阻斷劑對腦循環及記憶力之藥理作用，將近來年之文獻作一整理及討論。
並列摘要
Calcium ion is an important regulator of physiological functions for all cells. For executing these functions calcium ions are mobilized either from intracelluar pools or enter from the exterior. In resting cells free Ca^2+ levels are only about 0.1uM, ten thousandfold lower that extracellular levels. Calcium may enter cells via ”fast” or ”slow” channels. Fast, or receptor-operated channels (ROCs) are activated by the formation of ligand-receptor complex at the external surface of the cell membrane. Slow or voltage-operated channels (VOCs) are activated by ad hoc changes in membrane potential. There are complex regulatory systems supervising the equilibrium in the normal physiological state. In many pathophysiological situations. uncontrollred influx of ca1cium ions into the cells develops, causing a breakdown of the physiological extra-/intracellular concentration gradient: the cell are disregulated and lose their viability and biological activity. The cumulative consequences of this development are diverse pathological reactions. In recent years. calcium channel blockers or calcium antagonists have been developed to ameliorate those pathological events by diminishing the deleterious transfer of Ca^2+ ions across the membranes. These drugs mainly exert their effects on VOCs, at least three types of which have so far been identified: trient (T), longlasting (L), and neuronal (N). All three types of VOCs appear to be present on a wide variety of cells. Evidence has recently been presented that different tissues possess different forms (isoforms) of this calcium channel protein. The calcium channel blockers are also heterogenous in chemical origin and in preferential efficacy. The complexity and diversity would, at least in part, explain the different pharmacological effects in various tissues. This review will focus on the effects of calcium channel blockers on cerebral circulation and memory.