Blockade of voltage-dependent 42K efflux from rat brain synaptosome by minaprine and tetrahydroaminoacridine

Abstract

The effect of minaprine (3-(2-morpholinoethylamino)- 4-methyl-6-phenylpyridazine) on the K + channels was studied by means of 42K efflux from rat brain synaptosomes, comparing the effects of 4-aminopyridine and 9-amino-1,2,3,4-tetrahydroacridine (THA). 42K efflux from rat brain synaptosomes was classified into five components: a resting component (R), a rapidly inactivating, voltage-dependent component (T), a slowly inactivating, voltage-dependent component (S) and a voltage-dependent, Ca 2+-dependent component which is divided into a fast phase (C T) and a slower phase (C S). 4-Aminopyridine selectively inhibited 42K efflux of component T. THA blocked both S and T components. The inhibitory effect of THA on the 42K efflux of component S was quite pronounced compared with that of component T. Minaprine inhibited the 42K efflux of components S and T but the inhibitory effect on component S was observed with a lower dose of minaprine than that needed for the effect on component T. Minaprine had no effect on the Ca 2+-dependent component while THA blocked component C T. 42K efflux of the resting component was not changed by minaprine, THA or 4- aminopyridine. These results suggest that minaprine blocks Ca 2+ independent voltage-dependent K + channel is involved in the pharmacological actions of minaprine.