Receptors interaction with ligands

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). 

In addition to halopeiidol, the putative neuroleptics, limcazole (311), lemoxipiide (312), and gevotioline (313) bind to (7-ieceptois as does the dopamine uptake blocker, GBR 12909 (314) and two ligands active at the NMDA receptor, ifenprodil (315) and CNS 1102 (316). NPC 16377, (317) is a selective (7-teceptor ligand. MAO inhibitors and antidepressants also bind to (7-teceptors. Some evidence indicates that (7-teceptors in the brain are in fact a form of cytochrome which may account for the diversity of ligands interacting with (7-sites. 

Recently, numerous studies reported the application of homonuclear and heteronuclear selective recoupling schemes on uniformly labelled ligand interacting with membrane receptors. The polarization exchange curves were fitted with the two-spin model and showed that it is possible to determine intemuclear distances up to 4.5 A.118... 

The tetraantennary oligosaccharide illustrated in Figure 14.2 has been shown to present an umbrellalike structure as one of the major conformational populations.14,15 The distance between terminal sugar residues interacting with receptors may vary from 8 to 30 A. In the case of the phosphorylated high-mannose ligands for the MPR, the distance between phosphates is 15 A.16... 

Natural products are inherently bioactive. Bioactivity is a physiological response to a molecule or ion binding to a ligand, with downstream cascading consequences. Natural products are themselves products of enzymatic processes, demonstrating their ability to interact with receptors. Whether they bind other, nonsynthetic receptors likely depends on whether they have evolved in response to environmental pressures or whether they accumulate as a result of diverted primary metabolic pathways (Williams et al. 1989 Clardy 1995). 

The effects of a chemical in a tissue frequently depend on the chemical s interaction with cell surface or cytoplasmic receptors. In some cases, a chemical interacts directly with the cell membrane and alters its permeability. The pharmacodynamic actions of drugs are usually mediated by interactions with a receptor, and a drug often competes with endogenous ligands of a receptor. The toxicity of environmental chemicals can also depend on and be mediated by interactions with receptors. In some cases, the responses are different for chemical exposures at different fetal stages of development, and it is possible to explain the different responses by the chronology of the development of fetal receptor systems. The fetus may develop receptor systems for a compound before it develops the ability to metabolize that compound thus, a low level of an active chemical can have greater and more persistent effects in the fetus than in the mother, whose metabolism limits the duration and extent of the effect. This is one mechanism for selective developmental toxicity of chemicals. 

Portoghese, P.S., Alreja, B.D., Larson, D.L. Allylprodine analogues as receptor probes. Evidence that phenolic and nonphenolic ligands interact with different subsites on identical opioid receptors, J. Med. Chem. 1981, 24, 782-787. 

Leeson, P. D., Carling, R. W., James, K., Smith, J. D., Moore, K. W., Wong, E. H. F., Baker, R. Role of hydrogen binding in ligand interaction with the N-methyl-D-aspartate receptor ion channel, J. 

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