Mu opioid antagonists

Substitution of Trp by D-Trp increased the potency of somatostatin (101). Most other substitutions, however, are deleterious to biological activity. Cychc octapeptide analogues of somatostatin retain high potency one of them, CTOP, is a potent mu-opioid antagonist. 

McNichol ED et al Mu-opioid antagonists for opioid-induced bowel dysfunction. Cochrane Database Syst Rev 2008 Apr 16(2) CD006332. 

Jiang Q, Seyedmozaffari A, Sebastian A, Archer S, Bidlack JM (1995) Preventing morphine antinociceptive tolerance by irreversible mu-opioid antagonists before the onset of their antagonism. J Pharmacol Exp Ther 273 680-688... 

Kazmierski, W. Hruby, V.J. (1988) A New Approach to Receptor Ligand Design -Synthesis and Conformation of a New Class of Potent and Highly Selective Mu-Opioid Antagonists Utilizing Tetrahydroisoquinoline Carboxylic-Acid Tetrahedron, Vol. 44, No. 3, pp. 697-710. 

The intoxicating effects of opioids appear to be due to their action as agonists on mu (p) receptors of the opioid neurotransmitter system. Competitive p opioid antagonists such as naloxone and naltrexone acutely reverse many of the adverse effects of opioids. To date we do not have specific antagonists for most other abused substances, so rapid pharmacologic reversal of intoxication is usually not possible. 

Bot G, Blake A, Li S, Reisine T. Mutagenesis of a single amino acid in the rat mu opioid receptor discriminates the binding of full agonists from partial agonists and antagonists. J Neurochem 1998 70 358-365. 

Devine DP, Leone P, Wise RA. (1993). Mesolimbic dopamine neurotransmission is increased by administration of mu-opioid receptor antagonists. EurJ Pharmacol. 243(1) 55-64. 

Naloxone (75) is an opioid antagonist with slightly higher affinity for the mu subtype than kappa (A) in guinea-pig brain mu = 1.78 nM kappa = 27 nM delta = 1.72 nM) [96] and is widely used as a pharmacological tool to demonstrate the mechanism of action of opioid agonists. Despite much... 

Dooley, C. and Houghten, R. (Torrey Pines Institute for Molecular Studies) Novel mu opioid receptor ligands agonists and antagonists, W09640208 (1996) US5641861 (1997) US5919897 (1999). 

MODULATION OF THE MU OPIOID RECEPTOR BY DELTA-SELECTIVE 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... 

Tortella FC, Robles L, Holaday JW. The anticonvulsant effects of DADL are primarily mediated by activation of delta opioid receptors interaction between delta and mu-receptor antagonists. Life Sci 1985 37 497-503. 

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