[Behavioral studies of KSG-504, a new CCK-A receptor antagonist].
The effects of KSG-504 after intravenous administration on behavior and other central functions were studied. KSG-504 did not affect the general behavior of dogs up to the dose of 30 mg/kg, but the drug (100 mg/kg, i.v.) caused vomiting in 3 out of the 5 dogs. Moreover, KSG-504 (1-30 mg/kg, i.v.) had no effects on spontaneous motility, thiopental-induced sleep, acetic acid-induced writhing in mice and satiety in rats. A high dose of CCK-8 (100 micrograms/kg or more) suppressed spontaneous motility, writhing and satiety, and prolonged sleep when administered subcutaneously. The behavioral changes induced by CCK-8 were antagonized by KSG-504 in a dose-dependent manner (1-30 mg/kg, i.v.). When KSG-504 was administered intravenously to rabbits at the dose of 10 mg/kg or 0.5 mg/kg/min for 120 min, we could not detect the drug in the cerebrospinal fluid, indicating that KSG-504 does not cross the blood-brain barrier after peripheral administration of the drug. Thus, the inhibitory effect of KSG-504 on CCK-8-induced behavioral changes may be the result of antagonism at peripheral CCK-A receptors.
Yamazaki
Y
Y
Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan
Takeda
H
H
Akahane
M
M
Tsubaki
A
A
Ajisawa
Y
Y
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004285:Dogs; D004357:Drug Synergism; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D009281:Naphthalenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D010421:Pentanoic Acids / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D012844:Sincalide / Q000037:antagonists & inhibitors; D013874:Thiopental / Q000494:pharmacology
D009281:Naphthalenes; D010421:Pentanoic Acids; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C085253:KSG 504; D013874:Thiopental; D012844:Sincalide