Opioid antagonists delta-receptor selective

Spetea, M., Harris, H. E., Berzetei-Gurske, l. P., Klareskog, L., Schmidhammer, H. Binding, pharmacological and immunological profiles of the delta-selective opioid receptor antagonist HS 378, Life Sci. 2001, 69, 1775-1782. 

Portoghese P, Sultana M, Nagase H et al. A highly selective delta-1 opioid receptor antagonist 7-benzylidenenaltrexone. Eur J Pharmacol 1992 218 195-196. 

Page D, McClory A, Mischki T, Schmidt R, Butterworth J, St-Onge S, Labarre M, Payza K, Brown W. Novel Dmt-Tic dipeptide analogues as selective delta-opioid receptor antagonists. Bioorg Med Chem Lett 2000 10 167-170. 

Since at the time of the described studies it was thought that the two delta receptor antagonists naltriben (NTB) and 7-benzylidenenaltrexone (BNTX) were selective for the proposed delta-2 and delta-1 receptor subtypes, respectively [19], the relatively high affinity of NTB for the expressed receptors (as compared to BNTX, see Table 1) was thought to be consistent with the cloned human delta receptor being of the delta-2 opioid receptor subtype. 

The structures of selected peptide and nonpeptide delta-selective opioid antagonists are shown in Figure 1. However, although the compounds shown in Figure 1 have been introduced as neutral delta opioid antagonists, data from more sensitive functional assay systems have subsequently proven that these compounds are also capable of behaving as inverse agonists at the delta opioid receptor under appropriate conditions. 

BW373U86 were dose dependent and blocked by selective delta opioid receptor antagonists. 

Further studies in mouse vas deferens indicated that DPI-3290 is also active at mu opioid receptors. The intrinsic activity of DPI-3290 at mu opioid receptors was determined in the presence of the highly selective delta opioid receptor antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH) (3 pM) and the selective kappa opioid receptor antagonist nor-BNI (15 nM). Under these conditions, DPI-3290 again caused concentration-dependent inhibition of muscle contraction with a corresponding IC50 value of 6.2 2.0 nM. Although far less potent at kappa opioid receptors in comparison to its intrinsic activity at mu... 

The high-affinity GTPase activity in the mouse spinal cord is increased in a concentration-dependent manner by [D-Ala2]deltorphin II [82]. This increase of GTPase activity induced by [D-Ala2]deltorphin II is completely blocked by coincubation with a selective delta opioid receptor antagonist NTB [82]. 

Schiiier PW, Weltrowska G, Nguyen TM, et al. TIPP[nj] a highly potent and stable pseudopeptide 5 opioid receptor antagonist with extraordinary delta selectivity. J Med Chem 1993 36 3182-3187. 

Kamei J, Iwamoto Y, Suzuki T, Misawa M, Nagase H, Kasuya Y (1993) Antitussive effects of naltrindole, a selective delta-opioid receptor antagonist, in mice and rats. Eur J Pharmacol 249 161-165... 

Negus SS, Henriksen SJ, Mattox A, Pasternak GW, Portoghese PS, Takemori AE, Weinger MB, Koob GF. (1993). Effect of antagonists selective for mu, delta, and kappa opioid receptors on the reinforcing effects of heroin in rats. J Pharmacol Exp Ther. 265(3) 1245-52. 

The biochemical and pharmacological properties of the kappa receptor and the differences between the kappa, mu and delta receptors have been reviewed elsewhere. The reader is directed to the opioid review articles by Rees and Hunter (1990) [4], Casy (1989) [3] and Leslie (1987) [10] and also to two shorter reviews which deal specifically with kappa agonists the review by Horwell published in 1988 entitled Kappa Opioid Analgesics [8] and the review by Millan in 1990 on kappa opioid receptors and analgesia [9]. An account of the medicinal chemistry of selective opioid agonists and antagonists was published in 1990 by Zimmerman and Leander [5]. 

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