[Behavioral studies of KSG-504, a new CCK-A receptor antagonist].

Abstract

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.

• Authors: Y Yamazaki, H Takeda, M Akahane, A Tsubaki, Y Ajisawa
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 107 Issue 1 Pg. 21-31 (Jan 1996) ISSN: 0015-5691 [Print] Japan
• PMID: 8720295 (Publication Type: Journal Article)

Chemical References

• Naphthalenes
• Pentanoic Acids
• Receptor, Cholecystokinin A
• Receptors, Cholecystokinin
• KSG 504
• Thiopental
• Sincalide

Topics

• Animals
• Behavior, Animal (drug effects)
• Dogs
• Drug Synergism
• Female
• Male
• Mice
• Mice, Inbred ICR
• Motor Activity (drug effects)
• Naphthalenes (pharmacokinetics, pharmacology)
• Pentanoic Acids (pharmacokinetics, pharmacology)
• Rabbits
• Rats
• Rats, Wistar
• Receptor, Cholecystokinin A
• Receptors, Cholecystokinin (antagonists & inhibitors)
• Sincalide (antagonists & inhibitors)
• Thiopental (pharmacology)