Effects of a novel compound MCI-225 on impaired learning and memory in rats.
Effects of MCI-225, [4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-d]pyrimidine monohydrate hydrochloride] on experimental amnesia were studied in rats and compared with those of THA [9-amino-1,2,3,4-tetrahydroacridine]. In the Morris-type water maze task, MCI-225 (1-10 mg/kg, PO) reduced the spatial learning impairment induced by scopolamine (0.5 mg/kg, IP). In a passive avoidance (PA) task, administration of MCI-225 prior to training (1-30 mg/kg, PO) lessened the carbon dioxide (CO2)-induced amnesia in a dose-dependent manner. MCI-225 (1-100 mg/kg) did not affect gross behavior. THA (0.1-3 mg/kg, PO) reduced scopolamine-induced learning deficits in the water maze task, but the effect was not significant. THA (0.3-3 mg/kg, PO) also ameliorated the CO2-induced amnesia, although slightly, in the PA task. THA (10 mg/kg, PO) increased locomotor activity and higher dose of THA (30 mg/kg, PO) induced tremor, hypersalivation, and muscle relaxation. These results suggest that MCI-225 lessens impairments in learning and memory without causing serious behavioral abnormalities.
Eguchi
J
J
Pharmaceuticals Laboratory I, Research Center, Yokohama, Japan.
Yuasa
T
T
Egawa
M
M
Tobe
A
A
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002245:Carbon Dioxide; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D009043:Motor Activity / Q000187:drug effects; D009949:Orientation / Q000187:drug effects; D010879:Piperazines / Q000627:therapeutic use*; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine; D013619:Tacrine / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D010879:Piperazines; D011619:Psychotropic Drugs; D011743:Pyrimidines; C085298:MCI 225; D002245:Carbon Dioxide; D013619:Tacrine; D012601:Scopolamine