Antiamnesic and cholinomimetic side-effects of the cholinesterase inhibitors, physostigmine, tacrine and NIK-247 in rats.
The effects of physostigmine, tacrine and NIK-247 on scopolamine-induced impairment of a passive avoidance response were examined in rats. In addition, we investigated possible peripheral side-effects: miosis and salivation, and central side-effects: hypothermia and tremor which are mediated by cholinergic activation. Intraperitoneal injection of physostigmine reversed scopolamine-induced amnesia at a dose of 0.03 mg/kg. Antiamnesic effects of oral administration of tacrine and NIK-247 were observed at doses of 0.3 and 0.1-0.3 mg/kg, respectively. Intraperitoneal injection of physostigmine induced miosis, salivation, hypothermia and tremor at doses > or = 0.1, 0.3, 0.3 and 1 mg/kg, respectively. Oral administration of tacrine (at doses > or = 0.3 mg/kg) and NIK-247 (at doses > or = 3 mg/kg) produced miosis. Tacrine (at doses > or = 1 mg/kg) and NIK-247 (at doses > or = 3 mg/kg) produced hypersalivation. Hypothermia and tremor were observed after administration of tacrine (at doses > or = 10 mg/kg) and NIK-247 (30 mg/kg). The antiamnesic dose of physostigmine was 1/30-1/3 of doses with central or peripheral side-effects. The dose ratio of tacrine was 1/30-1; that of NIK-247 was 1/300-1/10. These results indicate that NIK-247 has higher safety and greater selectivity for cognitive functions than physostigmine or tacrine.
Yoshida
S
S
Omiya Research Laboratory, Nikken Chemicals Co., Ltd., Saitama, Japan.
Suzuki
N
N
D000284:Administration, Oral; D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002800:Cholinesterase Inhibitors; D007274:Injections, Intraperitoneal; D015877:Miosis / Q000139:chemically induced; D010830:Physostigmine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D012472:Salivation / Q000187:drug effects; D012601:Scopolamine / Q000633:toxicity; D013619:Tacrine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D014202:Tremor / Q000139:chemically induced
D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D011619:Psychotropic Drugs; D013619:Tacrine; D010830:Physostigmine; C049860:amiridine; D012601:Scopolamine