S-opioid receptors

A single residue, aspartate 95, in the S opioid receptor specifies high affinity agonist binding. J Biol Chem 1993 268 23055-23058. 

In October 2002, the FDA approved two new medications for treating opiate addiction, both developed by Reckitt Benckiser Pharmaceuticals. The new drugs, Subutex (buprenorphine hydrochloride) and Suboxone tablets (buprenorphine hydrochloride and naloxone hydrochloride) contain buprenorphine, a partial opioid agonist. Like methadone, buprenorphine binds to the brain s opioid receptors, but produces significantly reduced pleasurable effects than heroin. 

Kamei, J., Iwamaoto, Y., Suzuki, T., et al. Involvement of 8-,-opioid receptor antagonism in the antitussive effect of S-opioid receptor antagonists, Eur. J. Pharmacol. 1994, 257, 291-294. 

Kreil, G., Barra, D., Simmaco, M., Erspamer, V., Erspamer, G. F., Negri, L., Severini, C., Corsi, R., Melchiorri, P. Deltorphin, a novel amphibian skin peptide with high selectivity and affinity for S opioid receptors, Eur. J. Pharmacol. 1989, 162, 123-128. 

Putz, C.K., Straliburger, W., Zimmer, O., Englberger, W. (Grunenthal GmbH) Preparation of aryltetrahydroacridinemethanamines as S-opioid receptor ligands, EP970949 (1998). 

Sofuoglu, M., Portoghese, P.S., Takemori, A.E. Differential antagonism of Sopioid agonists by naltrindole and its benzofuran analog (NTB) in mice evidence for S opioid receptor subtypes, J. Pharmacol. Exp. Ther. 1991, 257, 676-680. 

It is the drug s sudden entry into the brain that accounts for the initial surge of energy. The rush is thought to last as long as it takes the brain and body to break heroin down into morphine, which is then absorbed by the body s opioid receptors. This stage finds the user going on the nod, an alternatively wakeful and pleasurably drowsy state that lasts four to six hours. 

Rational Drug Design of S Opioid Receptor Agonist TAN-67... 

An interesting comparison can be made looking at the a- and (5-tetralin derivatives entries—15/16 and —17 in Table 1 which can be regarded as cyclic confor-mationally constrained analogues of phenylglycine and phenylalanine. In an interesting study, 6-hydroxy-2-aminotetralin-2-carboxylic acid 12 (Hat) has been incorporated as a conformationally constrained tyrosine analogue into S-opioid receptor selective tetrapeptides.114 15 Whereas entry 15, the (S)-a-tetralin deriva-... 

Studies employing endpoints other than tail flick and hot plate have shown antinociceptive activity mediated through spinal S-opioid receptor... 

Endorphins are peptides produced by the intermediate pituitary that react with the brain s opioid receptors and presumably act as endogenous analgesics. The two best known endorphins from bovine brain are the pentapeptides, met-enkephalin and leu-enkephalin, whose structures are Tyr-Gly-Gly-Phe-Met and Tyr-Gly-Gly-Phe-Leu, respectively. There is evidence that the enkephalins, MSH, and ACTH are produced from the same precursor protein, pro-opiomelanocortin, molecular weight (MW) 31,000. This protein is present in both the anterior and intermediate pituitary glands. In the anterior pituitary area, this protein loses the element of ACTH (39 amino acids). In the intermediate pituitary, this protein... 

Quock RM, Burkey TH, Varga E, Hosohata Y, Hosohata K, Cowell SM, Slate CA, Ehlert FJ, Roeske WR, Yamamura HI (1999) The S-opioid receptor molecular pharmacology, signal transduction, and the determination of drug efficacy. Pharmacol Rev 52 503-532. 

A series of cyclic conformationally constrained peptides related to somatostatin were designed, synthesized and tested for opioid receptor interaction by Hruby and his collaborators. Compounds (17)-(22) were found to be pure opioid antagonists (GPI) with high affinity (IC50 = 1.2 to 4.3 nM) and exceptional selectivity for p over S opioid receptors (Table 3.1) and with minimal or no somatostatin-like activity (ligand binding assays)[63-65]. 

The concept of bridging has also been applied to antagonists bivalent ligands containing /3-naltrexamine pharmacophores (p. 67) linked by an oligoethylene glycol spanner have been described that differentially block /x, k, and S-opioid receptors.(198) Thus, 10a (with a six-ethylene-units spanner) most effectively blocks S-receptors (DADL on MVD), while 10b (with shorter spanner) acts preferentially at k-sites (ethylketazocine on GPI). 

Gacel G, Dauge V, Breuze P, Delay-Goyet P, Roques BP (1988) Development of conformation-ally constrained linear peptides exhibiting a high affinity and pronounced selectivity for S opioid receptors. J Med Chem 31 1891-1897... 

Figure 7.5. Ligands used to characterize S opioid receptors.

Portoghese PS, Sultana M, Takemori AE (1988) Naltrindole, a highly selective and potent non-peptide S-opioid receptor antagonist. Eur J Pharmacol 146 185-186... 

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