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• W1997748971 abstract "We found a potent and selective σ1 receptor agonist, SA4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride), with high affinity for the σ1 receptor subtype (IC50 = 17 nM), but low affinity for the σ2 receptor subtype (IC50 = 1800 nM). The binding activity and selectivity of SA4503 resembled those of (+)-pentazocine, a prototype σ1 receptor agonist. We have previously shown that the σ1 receptor agonist activated central cholinergic functions. Therefore, we examined the effects of SA4503 on the cholinergic dysfunction-induced memory impairments in a passive avoidance task. Scopolamine, a muscarinic acetylcholine receptor antagonist, produced memory impairment, when it was administered 30 min before the training session of the passive avoidance task in rats. Single administration of SA4503 significantly reduced the scopolamine-induced memory impairment. In addition, the lesioning by injection of α-amino-3-hydroxy-5-isoxazole acetic acid (ibotenic acid) into the basal forebrain area produced memory impairment in rats. Repeated administration of SA4503 after lesioning of the basal forebrain area ameliorated the basal forebrain lesion-induced memory impairment. Moreover, the ameliorating effect of SA4503 against the scopolamine-induced memory impairment was antagonized by both 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone (haloperidol), a σ receptor antagonist, and N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100), a putative σ1 receptor antagonist. These results suggest that SA4503 has an anti-amnesic effect against cholinergic dysfunction-induced memory impairment, and that the effect of SA4503 is mediated by the σ1 receptor subtype." @default.
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• W1997748971 date "1996-11-01" @default.
• W1997748971 modified "2023-09-26" @default.
• W1997748971 title "Ameliorating effect of SA4503, a novel σ1 receptor agonist, on memory impairments induced by cholinergic dysfunction in rats" @default.
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• W1997748971 doi "https://doi.org/10.1016/s0014-2999(96)00572-9" @default.
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