Gibson G E, Manger T
Cornell University Medical College, Burke Rehabilitation Center, White Plains, NY 10605.
Biochem Pharmacol. 1988 Nov 1;37(21):4191-6. doi: 10.1016/0006-2952(88)90115-3.
The effects of 1,2,3,4-tetrahydro-5-aminoacridine (THA), 4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP) on cytosolic free calcium (Ca2+i) were determined. Both 4-AP and THA have been used to treat Alzheimer's disease. THA is a structural analog of the aminopyridines, which alter calcium homeostasis in nerve terminals. The structural similarities between these compounds suggest a common mechanism of action. The aminopyridines raised Ca2+i concentrations in non-depolarized synaptosomes, whereas THA had no effect. Neither the aminopyridines nor THA had any effect on Ca2+i concentrations in potassium-depolarized synaptosomes. These results suggest that the beneficial effects of THA may be mediated by other mechanisms (i.e. neurotransmitter degradative enzyme inhibition), whereas those of 4-AP and 3,4-DAP may be due, at least in part, to their elevation of Ca2+i, which may enhance neurotransmitter release or other calcium-dependent processes.
测定了1,2,3,4-四氢-5-氨基吖啶（THA）、4-氨基吡啶（4-AP）和3,4-二氨基吡啶（3,4-DAP）对胞质游离钙（Ca2+i）的影响。4-AP和THA均已用于治疗阿尔茨海默病。THA是氨基吡啶的结构类似物，可改变神经末梢的钙稳态。这些化合物之间的结构相似性提示了一种共同的作用机制。氨基吡啶可提高非去极化突触体中的Ca2+i浓度，而THA则无此作用。氨基吡啶和THA对钾去极化突触体中的Ca2+i浓度均无影响。这些结果表明，THA的有益作用可能由其他机制介导（即抑制神经递质降解酶），而4-AP和3,4-DAP的作用至少部分可能归因于它们使Ca2+i升高，这可能增强神经递质释放或其他钙依赖性过程。
