Different peripheral and central antagonistic activity of new glutaramic acid derivatives on satiety induced by cholecystokinin in rats.
New glutaramic acid derivatives with cholecystokinin antagonistic activity were evaluated for their capacity to inhibit the satiety effect induced in the rat by intraperitoneal (i.p.) injection of cholecystokinin octapeptide (CCK-8). The most active compound, CR 1409, is about 4000 times more potent than proglumide when injected peripherally (i.p.). This compound competitively inhibits the action of CCK-8 at the receptor responsible for the satiety effect. In contrast, CR 1409, i.p. or intracerebroventricularly (i.c.v.) injected does not exhibit antagonistic effects when CCK-8 is administered i.c.v., confirming the existence of at least two different populations of CCK receptors.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005973:Glutamine / Q000031:analogs & derivatives*; D008297:Male; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000032:analysis / Q000502:physiology; D012527:Satiation / Q000187:drug effects*; D012844:Sincalide / Q000037:antagonists & inhibitors*
D011949:Receptors, Cholecystokinin; D005973:Glutamine; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide