Kobayashi_1996_J.Pharmacol.Exp.Ther_279_106

Reference

Title : Enhancement of acetylcholine release by SA4503, a novel sigma 1 receptor agonist, in the rat brain - Kobayashi_1996_J.Pharmacol.Exp.Ther_279_106
Author(s) : Kobayashi T , Matsuno K , Nakata K , Mita S
Ref : Journal of Pharmacology & Experimental Therapeutics , 279 :106 , 1996
Abstract :

We found that 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine dihydrochloride (SA4503), a potent and selective sigma 1 receptor agonist, significantly enhanced the cerebral acetylcholine (ACh) release in the rat using in vivo brain microdialysis technique. Interestingly, the significant enhancement of ACh release elicited by SA4503 was observed in the rat frontal cortex and hippocampus, although the striatal ACh release was unchanged. This cortical ACh release was fully reversed by haloperidol, a prototype sigma receptor antagonist, or by N, N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride, a putative sigma 1 receptor antagonist. In addition, this enhanced ACh release by SA4503 was inhibited by tetrodotoxin, a Na+ channel blocker. However, tetrahydroaminoacridine, an acetylcholinesterase inhibitor, significantly increased the extracellular ACh level in the rat frontal cortex and weakly increased the hippocampal level. This compound also showed the significant increase of extracellular ACh level in the rat striatum. Moreover, tetrahydroaminoacridine markedly produced cholinomimetic side-effects, such as hypothermia, tremor, miosis and lacrimation. However, SA4503 did not produce these cholinomimetic side-effects. These findings suggest that SA4503 enhances the ACh release that is mediated through a novel mechanism, namely sigma 1 receptor subtype. Furthermore, SA4503 has regional differences in the enhancement of cerebral ACh release, and did not produce cholinomimetic side-effects. These profiles are different from tetrahydroaminoacridine.

PubMedSearch : Kobayashi_1996_J.Pharmacol.Exp.Ther_279_106
PubMedID: 8858982

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Citations formats

Kobayashi T, Matsuno K, Nakata K, Mita S (1996)
Enhancement of acetylcholine release by SA4503, a novel sigma 1 receptor agonist, in the rat brain
Journal of Pharmacology & Experimental Therapeutics 279 :106

Kobayashi T, Matsuno K, Nakata K, Mita S (1996)
Journal of Pharmacology & Experimental Therapeutics 279 :106