Abstract: In some embodiments, the invention provides a non-addictive analgesic co-formulation comprising an opioid agonist in an amount sufficient to confer analgesia in a mammalian subject (such as a human) and a neutral opioid antagonist in an amount sufficient to inhibit peripheral effects of the opioid agonist, and insufficient to block substantial central effects of the opioid agonist in the subject. The formulation may be formulated for oral administration to the subject. Such formulations, and methods of using the same, may also deter diversion, inhibit peripheral effects of the opioid agonist, and reduce addiction liability.

Abstract: In some embodiments, the invention provides a non-addictive analgesic co-formulation comprising an opioid agonist in an amount sufficient to confer analgesia in a mammalian subject (such as a human) and a neutral opioid antagonist in an amount sufficient to inhibit peripheral effects of the opioid agonist, and insufficient to block substantial central effects of the opioid agonist in the subject. The formulation may be formulated for oral administration to the subject. Such formulations, and methods of using the same, may also deter diversion, inhibit peripheral effects of the opioid agonist, and reduce addiction liability.

Abstract: A non-addictive analgesic co-formulation comprising an opioid agonist in an amount sufficient to confer analgesia in a mammalian subject and a neutral opioid antagonist in an amount sufficient to inhibit peripheral effects, and insufficient to block substantial central effects, of the opioid agonist in the subject. Such formulations, and methods of using same, may also deter diversion, inhibit peripheral effects, and reduce addiction liability.

Abstract: In some embodiments, the invention provides a non-addictive analgesic co-formulation comprising an opioid agonist in an amount sufficient to confer analgesia in a mammalian subject (such as a human) and a neutral opioid antagonist in an amount sufficient to inhibit peripheral effects of the opioid agonist, and insufficient to block substantial central effects of the opioid agonist in the subject. The formulation may be formulated for oral administration to the subject. Such formulations, and methods of using the same, may also deter diversion, inhibit peripheral effects of the opioid agonist, and reduce addiction liability.

Abstract: Methods of utilizing an opioid agonist in a mammalian subject in a manner that inhibits peripheral effects of the opioid agonist are described. The methods comprise administering the opioid agonist in an amount sufficient to confer analgesia the subject and co-administering a neutral opioid antagonist or pharmaceutically acceptable isomorph or pharmaceutically acceptable salt thereof in an amount sufficient to substantially inhibit peripheral effects and insufficient to block substantial central effects of the opioid agonist in the subject.

Abstract: The clinical outcome of disseminated melanoma is grim. Small molecular weight antagonists (preferably about seven amino acid residues) specific for MCR on melanoma cells are provided for the therapy of melanoma as well as in other conditions where modulation of MCR is of clinical significance. A particularly preferred antagonist is p-anisoyl-[D-Arg6,9, D-Lys11, D-Leu12] dynorphin A(6-12)-NH2, which is an excellent antagonist of the MCR-1 receptor.

Abstract: The invention relates to the use of naltrexone and naloxone analogs, which are neutral antagonists at the &mgr; opioid receptor, for the treatment of drug dependency in a drug-dependent individual. Surprisingly, it has been found that administration of a therapeutically effect amount of the naloxone or naltrexone analogs described herein for the treatment of a drug dependency, can result in reduction of undesirable side effects resulting from current treatments using naloxone and naltrexone. For example, the treatment described herein can result in a reduction in the withdrawal symptoms and aversion encountered in the use of naloxone and naltrexone in the treatment of drug dependency. In addition, the naltrexone and naloxone analogs of the invention can be used for the treatment of pain in an individual in need thereof by modulating opoid pain treatment using neutral antagonists, for example, reversing respiratory depression withough causing other adverse effects.

Abstract: A method for screening G protein coupled receptors is provided in which G protein coupled receptors that are constitutively active are determined, such as by measuring receptor phosphorylation agonist independent signaling. When a G protein coupled receptor is found to be regulated by constitutive activity, then assay systems may be set up to classify test compounds as agonists, neutral antagonists, or negative antagonists with respect to G protein coupled receptor signaling and phosphorylation. Such determinations and screening are useful for selecting new pharmaceuticals potentially useful in treating disease states mediated by & protein coupled receptors, with applications including treatments in conjunction with narcotic analgesia.

Abstract: The clinical outcome of disseminated melanoma is grim. Small molecular weight antagonists (preferably about seven amino acid residues) specific for MCR on melanoma cells are provided for the therapy of melanoma as well as in other conditions where modulation of MCR is of clinical significance. A particularly preferred antagonist is p-anisoyl-[D-Arg6,9, D-Lys11, D-Leu12] dynorphin A(6-12)-NH2, which is an excellent antagonist of the MCR-1 receptor.