Protective effects of indeloxazine hydrochloride on cerebral ischemia in animals.
Effects of indeloxazine hydrochloride [(+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride, YM-08054] on cerebral ischemia were investigated in animals. Indeloxazine prolonged the gasping duration dose-dependently in decapitated mice. Bilateral occlusion of the carotid artery for 5 min shortened the latency of step-through in passive avoidance task 4 days following ischemia in mongolian gerbils. The i.p. administration of indeloxazine was started just after the surgical operation and repeated twice a day for 4 days. Indeloxazine (2 mg/kg) significantly prolonged the latency of step-through in this amnesic model, indicating a reversal effect on the ischemia-induced amnesia. In biochemical studies, decreases in brain ATP and total adenine nucleotide levels were inhibited by indeloxazine (2 mg/kg i.p., once a day for 7 days) in four-vessel occluded rats. These findings indicate that indeloxazine possesses protective effects on cerebral ischemia presumably due, in part, to improvement of the cerebral energy metabolism.
Yamamoto
M
M
Department of Pharmacology, Yamanouchi Pharmaceutical Co., Ltd. Tokyo, Japan.
Shimizu
M
M
Sakamoto
N
N
Ohtomo
H
H
Kogure
K
K
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005849:Gerbillinae; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009025:Morpholines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009025:Morpholines; C020852:indeloxazine