Blockade of voltage-dependent 42K efflux from rat brain synaptosome by minaprine and tetrahydroaminoacridine.
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 (CT) and a slower phase (CS). 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 CT. 42K efflux of the resting component was not changed by minaprine, THA or 4-aminopyridine. These results suggest that minaprine blocks Ca2+ independent voltage-dependent K+ channel is involved in the pharmacological actions of minaprine.
Chaki
S
S
Department of Pharmacology, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Muramatsu
M
M
Otomo
S
S
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D013619:Tacrine / Q000494:pharmacology*
D000928:Antidepressive Agents; D015221:Potassium Channels; D011724:Pyridazines; C006149:minaprine; D013619:Tacrine; D015761:4-Aminopyridine; D011188:Potassium