Cholecystokinin B receptor

Newel experimental approaches to anxiety therapy include ligands interacting with the ligand-gated ion channels that are selectively activated by nicotine, C qH 4N2 (87), the well-known active ingredient of cigarettes which has anxiolytic actions (42). Cholecystokinin B receptor ligands, specifically the dipeptoid, CI-988 [130404-91 -0] 02 1142 40 (88) have demonstrated anxiolytic activity ia preclinical models (43). 

Hamilton SP, Slager SL, Helleby L, Heiman GA, Klein DF, Hodge SE, Weissman MM, Fyer AJ, Knowles JA (2001) No association or linkage between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B receptor and panic disorder. Mol Psychiatry 6 59-65... 

Frankland PW, Josselyn SA, Bradwejn J, Vaccarino FJ, Yeomans JS (1997) Activation of amygdala cholecystokinin B receptors potentiates the acoustic startle response in the rat. J Neurosci 17 1838-1847... 

Schematic diagram of one model of the physiologic control of hydrogen ion secretion by the gastric parietal cell. ECL cell, enterochromaffin-like cell G(CCK-B), gastrin-cholecystokinin-B receptor H, histamine H2, histamine H2 receptor Mi, M3, muscarinic receptors ST2, somatostatin2 receptor ATPase, K /H ATPase proton pump. Some investigators place histamine receptors—and possibly cholinoceptors—on nearby tissue cells rather than on the parietal cell itself. (Modified and redrawn from Sachs G, Prinz C Gastric enterochromaffin-like cells and the regulation of acid secretion. News Physiol Sci 1996 11 57, and other sources.)...

Path A leads to tryptophan derivatives (116), some of which are potent cholecystoki-nin antagonists (73). Some quinazolinone derivatives (117) of disconnection pathway B showed extremely high potency and excellent selectivity as cholecystokinin-B receptor sub-type ligands (44). A combination of X-ray crystallography and computational chemistry was used in the decision-making process in the bond disconnection (44) and in the design cf the specific target molecules. 

BEHR, T.M., BEHE, M., Cholecystokinin-B/gastrin receptor-targeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptor-expressing malignancies, Semin. Nucl. Med. 32 (2002) 97-109. 

Opponents of MCS argue that behavioral and stress-mediated mechanisms control the symptoms. They claim that MCS most likely represents the overlapping of primary psychiatric disorders, misdiagnosed medical disorders, and classical conditioning. One study found significantly increased prevalence of the panic disorder-associated cholecystokinin B receptor allele 7 in subjects with MCS (Binkley et al. 2001). Three opposing interpretations of MCS are that... 

Binkley K, King N, Poonai N, et al Idiopathic environmental intolerance increased prevalence of panic-disorder-associated cholecystokinin B receptor allele 7. J Allergy Clin Immunol 107 887-890, 2001... 

For the synthesis of cholecystokinin-B receptor antagonists by Lowe III and coworkers [70], the amino benzazepin-2-one (47) was resolved into single stereoisomers by the protocol shown in Scheme 5.21 (for clarity, only single stereoisomers depicted). The notable feature in this instance is the selective removal of the L-phenylalanine auxiliary by Edman degradation in the presence of additional amide linkages. 

In the synthesis of Cholecystokinin-B receptor antagonists, a benzodiazepin intermediate bearing an isocyanato group plays a key role. It is prepared from the corresponding amine 423 by carbonylation with phosgene in 98% yield [292]. 

Lowe IIIJA, Hageman DL, Drozda SE, McLean S, Bryce DK, Crawford RT, Zorn S, Morrone J, Bordner J. 5-Phenyl-3-ureidobenzazepin-2-ones as cholecystokinin-B receptor antagonists./. Afefi . Chem. 1994 37(22) 3789-3811. 

Archer-Lahlou, E. Tikhonova, I. Escrieut, C. Dufresne, M. Seva, C. Clerc, P. Pradayrol, L. Moroder, L. Maigret, B. Fourmy, D., Modeled structure of a G-protein-coupled receptor the cholecystokinin-1 receptor, J. Med. Chem. 2005, 48, 180-191. 

HGnn, J. Maigret, B. Tarek, M. Escrieut, C. Fourmy, D. Chipot, C., Probing a model of a GPCR/ligand complex in an explicit membrane environment. The human cholecystokinin-1 receptor, Biophys. J. 2006, 90, 1232-1240. 

Bradwejn J, Koszycki D, Payeur R Study of the replication of action of cholecystokinin in panic disorders. Am J Psychiatry 149 962-964, 1992c Bradwejn J, Koszycki D, Couetoux-Dutertre AC, et al L-365,260, a CCK-B receptor antagonist, blocks CCK-4 panic (oral presentation). Presented at the annual meeting of the Anxiety Disorders Association of America (NR 235), Charleston, SC, March 20, 1993... 

Huganir RL, Greengard P Regulation of neurotransmitter receptor desensitization by protein phosphorylation. Neuron 5 555-567, 1990 Hughes J, Boden P, Costall B, et al Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc Natl Acad Sci U S A 87 6728-6732, 1990... 

Lee YM, Beinbom M, McBride EW, et al The human brain cholecystokinin-B/gastrin receptor cloning and characterization. J Biol Chem 268 8164-8169, 1993 Legris P, George Y, Boval P, et al A comparative study of alpidem versus Buspirone, in Imidazopyridines in Anxiety Disorders A Novel Experimental and Therapeutic Approach. Edited by Barthohni G, Garreau M, MorseUi PL. New York, Raven, 1993, pp 183-192... 

The gastrin receptor is one of the receptors that bind cholecystokinin (Table 13.4), and is known as the CCK-B receptor it is another member of the G-protein-coupled receptor family. 

Cholecystokinin. Cholecystokinin (CCK) is one of the most abundant neurotransmitters in the central nervous system. Two CCK receptor subtypes have been cloned to date, that is, CCK-A (Alimentary), which are primarily located in the periphery, and CCK-B (Brain) (219). CCK-B receptors are widely distributed throughout the brain, but have particularly high densities in the hypothalamus, limbic system, basal ganglia, hippocampus, and brain stem (219). CCK-4 (a tetrapeptide) and CCK-8S (a sulfated oc-... 

BEHR, T.M., et al.. Targeting of cholecystokinin-B/gastrin receptors in vivo Preclinical and initial clinical evaluation of the diagnostic and therapeutic potential of radiolabelled gastrin, Eur. J. Nucl. Med. 25 (1998) 424-430. 

A. Bado, C. Garbay, B.P. Roques, Structure-based design of new constrained cyclic agonists of the cholecystokinin CCK-B receptor,... 

Fig. 28.9 Structural formulae Of benzodiazepines active at human and rodent cholecystokinin/gastrin B receptors.

Beinhrom, M., Lee, Y.-M., McBride, E.W., Quinn, S.M. and Kopin, A.S. (1993) A single amino acid of the cholecystokinin-B 1 gastrin receptor determines specificity for non-peptide antagonists. Nature 362 348-351. 

One of the important commercial routes to 1,4-benzodiazepines from 2-aminobenzophenones involves reaction of an AT-acylated analogue bearing a leaving group in the acyl chain with a source of ammonia <84CHEC-I(7)593>. One example of this reaction was used to synthesize an intermediate (140) for a cholecystokinin type B receptor antagonist (Equation (7)) <93BMC1919>. 

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