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  • Title: Changes in cytosolic free calcium with 1,2,3,4-tetrahydro-5-aminoacridine, 4-aminopyridine and 3,4-diaminopyridine.
    Author: Gibson GE, Manger T.
    Journal: Biochem Pharmacol; 1988 Nov 01; 37(21):4191-6. PubMed ID: 2847755.
    Abstract:
    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.
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