CCKB antagonists

Kramer MS, Cutler NR, Ballenger JC, et al A placebo-controUed trial of L-365,260, a CCKB antagonist, in panic disorder. Biol Psychiatry 37 462-466, 1995 Krauss GL, Fisher RS Cerebellar and thalamic stimulation for epilepsy, in Electrical and Magnetic Stimulation of the Brain and Spinal Cord. Edited by Devinsky O, Beric A. New York, Raven, 1993, pp 231-245 Krell RD, Goldberg AM Effect of acute and chronic administration of lithium on steady-state levels of mouse brain choline and acetylcholine. Biochem Pharmacol 22 3289-3291, 1973... 

Boden, P.R. et al. (1993) Cholecystokinin dipeptoid antagonists Dest, synthesis, and anxiolytic profile of some novel CCKA and CCKB selective aird mixed CCKA/CCKB antagonists. / Med. Chem.. 36. 552-565. 

The utility of this approach is exemplified by the synthesis of [carbonyl- " C]L-740,093 (29), a urea type CCKB antagonist, and of [carbonyl- " C]EPTC 30, a thiocarbamate type herbicide. Furthermore the synthesis of 21 demonstrates that it can also be exploited... 

In humans, CCKb receptor ligands can induce a panic attack, especially in panic patients, whereas antagonists (e.g. CL988) have the opposite effect. Nevertheless, the results from clinical trials of this compound are not promising, mainly due to low bioavailability and unacceptable side-effects. 

Izumi T, Inoue T, Tsuchiya K, Hashimoto S, Ohmori T, Koyama T (1996) Effect of the selective CCKB receptor antagonist LY288513 on conditioned fear stress in rats. Eur J Pharmacol 300 25-31... 

Proglumide (Milid) acts as a cholecystokinin antagonist, blocking both the CCKa and CCKb subtypes. It was used mainly in the treatment of stomach ulcers but has now been largely replaced by newer drugs. 

Singh, L. ef al. (1995) Peptoid CCK receptor antagonists Pharmacological evaluation of CCKa. CCKb and mixed CCKa/b receptor antagonists, Eur, J. Pharmacol.. 286,185-191. 

Cl 988 is a complex tricyclo-indolyl structure, a selective (CCKb) CHOLECYSTOKININ RECEPTOR ANTAGONIST, used as a pharmacological tool. 

LY 288513 is a pyrazolidinecarboxamide derivative, a (CCKB-Subtype) CHOLECYSTOKININ RECEPTOR ANTAGONIST. It shows experimental ANXIOLYTIC and ANTIPSYCHOTIC activity, and has advanced to early clinical trials stage. Lyclear permethrin. 

YM022 is a benzodiazepine, a selective (CCKB/gastrin subtype) cholecystokinin receptor antagonist. It is used as a pharmacological tool. 

Infusion of CCK4 (an agonist at CCKb receptors) induces panic. CCKb receptor antagonists anxiolytic in some animal models. 

---