The suppression of potassium cyanide-induced mortality by the increase of extracellular acetylcholine level in the brain.
We examined whether potassium cyanide (KCN)-induced mortality in mice was regulated by acetylcholine transmission in the brain. Our novel compound, (+/-)-1-(1,2-diphenyl)ethyl-4-[2-(3,4-dimethoxyphenyl)ethyl]piperazine dihydrochloride (SA3251), suppressed KCN-induced mortality in mice. In parallel, SA3251 increased the cortical and hippocampal extracellular acetylcholine level in conscious, freely-moving rats. Interestingly, the time course patterns of these two events induced by SA3251 correlated. These results suggest that the central cholinergic system plays an important role in the suppression of KCN-induced mortality.
Senda
T
T
Central Research Laboratories, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Matsuno
K
K
Mita
S
S
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000517:prevention & control; D008297:Male; D051379:Mice; D017551:Microdialysis; D010879:Piperazines / Q000494:pharmacology*; D011190:Potassium Cyanide / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
C417089:1-(1,2-diphenyl)ethyl-4-(2-(3,4-dimethoxyphenyl)ethyl)piperazine; D010879:Piperazines; D011190:Potassium Cyanide; D000109:Acetylcholine