Cholinomimetic activity of minaprine is related to the amelioration of delayed neuronal death in gerbils.
We attempted to determine if the cholinomimetic activity of the psychotropic drug minaprine was related to the amelioration of the delayed neuronal death induced by cerebral ischemia in Mongolian gerbils. Minaprine improved the passive avoidance deficit induced by cerebral ischemia, and the histopathological ischemic neuronal changes in the hippocampal CA1 neurons were diminished. These effects were completely inhibited by treatment with the cholinergic blocker scopolamine. Rectal temperature fell about 1.5 degrees C immediately after cerebral ischemia and hyperthermia occurred 30 and 60 min after recirculation. Minaprine had no effect on body temperature before or after ischemia. Physostigmine and tetrahydroaminoacridine (THA), drugs which stimulate the cholinergic system, improved passive avoidance deficits and prevented the delayed neuronal death. These effects of physostigmine and THA were completely inhibited by scopolamine. Pentobarbital and diazepam also improved the passive avoidance deficit and prevented the destruction of CA1 neurons. In contrast with minaprine, these effects of pentobarbital and diazepam were not inhibited by scopolamine. As the protective effect of minaprine against ischemia-induced delayed neuronal death is related to cholinomimetic activities, these events differ from those seen with pentobarbital and diazepam.
Karasawa
Y
Y
Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Araki
H
H
Otomo
S
S
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002339:Carotid Arteries / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D005849:Gerbillinae; D006624:Hippocampus / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010277:Parasympathomimetics / Q000494:pharmacology*; D011724:Pyridazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D010277:Parasympathomimetics; D011724:Pyridazines; C006149:minaprine