Opioid peptides receptor antagonists

A 17 amino acid long peptide sequentially related to opioid peptides in particular dynorphin A. OFQ/N is inactive at the 5, k, and p opioid receptors, but binds to its own NOP receptor (formerly ORL-1, for opioid receptor like-1). In contrast to opioid peptides, OFQ/N has no direct analgesic properties. OFQ/N is the first example for the discovery of a novel neurotransmitter from tissue extracts by using an orphan receptor as bait. Centrally administered in rodents, OFQ/N exerts anxiolytic properties. OFQ/N agonists and antagonists... 

Opioid peptides, 17 (1980) 1 receptor antagonists, 35 (1998) 83 receptor-specific analogues, 28 (1991)... 

Corbett AD, Gillan MGC, Kosterlitz HW, McKnight AT, Paterson SJ, Robson LE. Selectivities of opioid peptide analogues as agonists and antagonists at the 6-receptor. Br J Pharmacol 1984 83 271-279. 

Schiller PW, Weltrowska G, Schmidt R, Berezowska I, Nguyen TM-D, Lemieux C, Chung NN, Carpenter KA, Wilkes BC. Subtleties of structure-agonist versus antagonist relationships of opioid peptides and peptidomi-metics. J Receptor Signal Transduction Res 1999 19 573-588. 

The efficacy and strength of opioid antagonists varies depending on the type of opioid receptors (u-, 8-, K-, a-) with which they interact. The mechanism of their action is not fully clear. However, it has been suggested that they antagonize the action of endogenous opioid peptides. 

Nalorphine and levallorphan are examples. For example in patients with postoperative pain the analgesic effects of 10 mg of nalorphine is about the same as 10 mg of morphine. On the other hand naloxone and naltrexone seem to have no agonistic activity and some antagonistic affinity for all types of opioid receptors. Although antagonists could be expected to have effects by altering the actions of endogenous opioid peptides mostly such effects are not discernable. 

Comparative substructural elements of peptide and nonpeptide ligands i-opioid receptor agonists, angiotensin, and NPY receptor antagonists... 

Figure 1 Non-peptidic tool compounds for the 5 opioid receptor (antagonists).

Portoghese, P.S., Sultana, M., Nagase, H., Takemori, A.E. Application of the message-address concept in the design of highly potent and selective non-peptide 8 opioid receptor antagonists, J. Med. Chem. 1988, 31, 281-282. 

Endogenous opioid peptides. Extensive processing is also involved in formation of analgesic opioid peptides, which are present naturally in the brain (see also Section B). Tire formation of (1-endorphin in the hypothalamus from prepro-opiomelanocortin (Fig. 30-2) has already been mentioned. Prior to the discovery of P-endorphin, the pentapeptides Met-enkephalin and Leu-enkephalin (Table 30-4) were discovered and were found to compete with opiate drugs for receptors in the brain. Tire larger P-endorphin, which contains the Met-enkephalin sequence at its N terminus, is a far more potent opiate antagonist than are the enkephalins. Since the Met-enkephalin sequence within P-endorphin is not flanked by basic residues, it apparently is normally not released. Two other recently discovered brain peptides are endomorphin-1 (YPWF-NH2) and endomorphin-2 (YPFF-NH2). They are also potent agonists for the opioid receptors, especially the p receptor (see Section B,10).,61a,61b... 

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