Non-peptide agonists

The peptides will now be considered individually in some detail. It must be noted that the large molecular size of the peptides means that they are even less likely to cross the blood-brain barrier than classical transmitters and the instability of peptides means that full functional studies require non-peptide agonists and antagonists. Whereas nature has provided morphine and medicinal chemists have made naloxone, tools are lacking for many other peptides. 

Human delta opioid receptor Functional studies on stably transfected Chinese hamster ovary cells after acute and chronic treatment with the selective non-peptidic agonist SNC-80. J Pharmacol Exp Ther 1996 278 1083-1089. 

NMR, protein structure determination, 23, 275 non-enzymatic glycosylation, 14, 261 non-HIV antiviral agents, 36, 119, 38, 213 non-nutritive, sweeteners, V7, 323 non-peptide agonists, 32, 277 non-peptidic d-opinoid agonists, 37,159... 

Another interesting aspect of the non-peptide agonist/antagonist structure-activity studies has been the identification of both agonists and antagonists in the same series of compounds by minor structural modifications. For example. 

Bishop MJ, Garrido DM, Boswll GE et al (2003) 3-(aR)-a((2S,5R)-4-Allyl-2,5-dimethyl-l-piperazinyl)-3-hydroxybenzyl)-A-alkyl-A-arylbenzamides potent, non-peptidic agonists of both the p and 5 opioid receptors. J Med Chem 46 623-633... 

Liao S, Alfaro-Lopez J, Shenderovich MD et al (1998) De novo design, synthesis, and biological activities of high-affinity and selective non-peptide agonists of the delta-opioid receptor. J Med Chem 41 4767-4776... 

There is enormous activity worldwide seeking to identify non-peptide agonists or antagonists for both the peptide receptors and the orphans, since it is expected that this will be a fruitful area for drug discovery. Witness the success of the non-peptide angiotensin II receptor antagoifists (collectively known as the sartans ) approved several years ago for the treatment of hypertension. 

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