40 results about "Mu Opiate Receptor" patented technology

This invention relates to a method of selectively enhancing the analgesic potency of morphine and other clinically used bimodally-acting opioid agonists and simultaneously attenuating development of physical dependence, tolerance and other undesirable side effects caused by the chronic administration of said bimodally-acting opioid agonists comprising the co-administration of a bimodally-acting opioid agonist which activates both inhibitory and excitatory opioid receptor-mediated functions of neurons in the nociceptive (pain) pathways of the nervous system and an opioid receptor antagonist which selectively inactivates excitatory opioid receptor-mediated side effects. This invention also relates to a method of using excitatory opioid receptor antagonists alone to block the undesirable excitatory side effects of endogenous bimodally-acting opioid agonists which may be markedly elevated during chronic pain. This invention further relates to a method of long-term treatment of previously detoxified opiate, cocaine and alcohol addicts utilizing said excitatory opioid receptor antagonists, either alone or in combination with low-dose methadone, to prevent protracted physical dependence, and to compositions comprising an excitatory opioid receptor antagonist of the invention and a bimodally-acting opioid agonist.

Methods and pharmaceutical compositions of matter are disclosed and claimed relating to cardioprotective effect mediated by delta ( delta ) opioid receptor agonists or more specifically delta-1 ( delta 1)-opioid receptor agonists. Further, methods drawn to reducing ischemic damage to organs and tissues having delta ( delta ) opioid receptor agonists or more specifically delta-1 ( delta 1)-opioid receptors are disclosed and claimed. Specifically, methods and pharmaceutical compositions of matter are taught as a means of providing cardioprotective treatment through the administration of delta ( delta ) opioid receptor agonists or more specifically delta-1 ( delta 1)-opioid receptor agonists, such as TAN67(-). Said methods and pharmaceutical compositions are envisioned as a means of reducing myocardial infarction arising from the onset and sequelae of myocardial ischemia.

The invention provides for compositions and methods of reducing pain in a subject by administering a combination of mu-opioid receptor agonist, kappa1-opioid receptor agonist and a nonselective opioid receptor antagonist in amounts effective to reduce pain and ameliorate an adverse side effect of treatment combining opioid-receptor agonists. The invention also provides for methods of enhancing an analgesic effect of treatment with an opioid-receptor agonist in a subject suffering from pain while reducing an adverse side effect of the treatment. The invention also provides for methods of reducing the hyperalgesic effect of treatment with an opioid-receptor agonist in a subject suffering from pain while reducing an adverse side effect of the treatment. The invention further provides for methods of promoting the additive analgesia of pain treatment with an opioid-receptor agonist in a subject in need while reducing an adverse side effect of the treatment.

Particles comprising an opioid receptor antagonist as well as methods of their use and methods of their preparation are provided herein. Such particles may be used for treating and preventing opioid-induced side effects in patients, and may be provided to chronic opioid users as well.

Opioid receptors form functional heterodimers with each other and with other G-protein coupled receptors, such as dopamine receptors, adrenergic receptors, or chemokine receptors. These receptors can be exploited for high throughput screening of compounds to identify heterodimer opioid receptor modulators (agonists and antagonists). The invention also relates to identification of novel heterodimer receptor ligands and synergistic compositions, which can provide strategies for analgesia, narcotic addiction, hypertension, HIV infection, and immune system function.

A compound of the formula (I) or a pharmaceutically acceptable salt, enantiomer, racemate, diastereomers or mixtures thereof, or a solvate thereof, formulations and methods of use thereof, as opioid receptor antagonists are disclosed wherein the variables are as described herein.

The application is directed to compounds of Formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, Y, Z, and G are defined as set forth in the specification. The invention is also directed to use of compounds of Formula (I), and pharmaceutically acceptable salts and solvates thereof, to treat disorders responsive to the modulation of one or more opioid receptors, or as synthetic intermediates. Certain compounds of the present invention are especially useful for treating pain.

The present invention features compositions for intranasal administration comprising an opioid receptor antagonist. The invention also features methods of using such compositions in the treatment of various diseases and disorders, such as the treatment of alcoholism. In certain embodiments, the opioid receptor antagonist is naltrexone or a pharmaceutically acceptable salt thereof.

A compound of the formula (I) (I) wherein the variables X1 to X6, Ra, Rb, R1 to R7 including R3′, E, p, j, y, z, A, B and C are as described or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed

The present invention relates generally to analgesic compounds having a mu opioid receptor agonist linked to a delta opioid receptor antagonist, and to methods for producing analgesia using such compounds. As compared to opioids such as morphine, these compounds can cause less tolerance, physical dependence, and / or constipation. These compounds are also more potent than morphine and are able to cross the blood brain barrier, thereby allowing for peripheral (e.g., IV) administration.

The present invention pertains to novel uses of endomorphine-1 peptide, analogs, and salts thereof for therapy of children, patients currently suffering from drug addiction, patients prone to opioid addiction, and patients with chemo-induced pain.

A topical opioid paradigm was developed to determine analgesic peripheral effects of morphine. Topical morphine as well as peptides such as [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO) produced a potent, dose-dependent analgesia using the radiant heat tailflick assay. The topical drugs potentiated systemic agents, similar to the previously established synergy between peripheral and central sites of action. Local tolerance was rapidly produced by repeated daily topical exposure to morphine. Topical morphine tolerance was effectively blocked by the N-Methyl-D-Aspartate (NMDA) receptors antagonist MK801 and ketamine given either systemically or topically. NMDA receptor antagonists reversed pre-existing morphine tolerance. The activity of topical NMDA antagonists to block local morphine tolerance suggests that peripheral NMDA receptors mediate topical morphine tolerance. Morphine was cross tolerant to [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO), but not to morphine-6 beta -glucuronide, implying different mechanisms of action. These observations have great importance in the design and use of opioids clinically. Topical pharmaceutical compositions comprising an analgesic that functions through an opiate receptor and an NMDA receptor antagonist for producing analgesia without inducing tolerance are described.

Indole alkaloid derivatives having an opioid receptor agonistic effect, their synthesis, and therapeutic compositions containing these derivatives, and methods of treating conditions with these compounds and therapeutic compositions, are provided.

Combinations comprise a therapeutically effective amount of one or more stimulants and and / or pharmaceutically acceptable analogs, salts, or hydrates of the one or more stimulants, and one or more non-selective opioid receptor antagonists, and / or pharmaceutically acceptable analogs, salts or hydrates of the one or more non-selective opioid receptor antagonists. These combinations may be used for treating obesity via administration to a subject having a need thereof.

The present invention relates to a series of substituted compounds having the general formula (I), including their stereoisomers and / or their pharmaceutically acceptable salts. (I) Wherein A, m, R1s, R2, R3, R4 are as defined herein. This invention also relates to methods of making these compounds including intermediates. The compounds of this invention are effective at the kappa (κ) opioid receptor (KOR) site. Therefore, the compounds of this invention are useful as pharmaceutical agents, especially in the treatment and / or prevention of a variety of central nervous system disorders (CNS), including but not limited to acute and chronic pain, and associated disorders, particularly functioning peripherally at the CNS.

The invention relates to cyclic peptide agonists that bind to the mu (morphine) opioid receptor and their use in the treatment of acute and / or chronic pain. Embodiments of the invention are directed to cyclic pentapeptide and hexapeptide analogs of endomorphin that have (i) a carboxy-terminal extension with an amidated hydrophilic amino acid and (ii) a substitution in amino acid position 2. These peptide analogs exhibit decreased tolerance relative to morphine, increased solubility compared to similar tetrapeptide analogs, while maintaining favorable or improved therapeutic ratios of analgesia to side effects.

The present invention is directed to a method of treating or preventing an addictive behavior in a subject, said method comprising administering to said subject an effective amount of a dopamine antagonist and a opiate receptor antagonist or a composition comprising same. Further provided are pharmaceutical compositions comprising, as active substances, at least one dopamine antagonist and at least one opiate receptor antagonist.

A compound of the formula (I) wherein the variables X1, X2, R1 to R7 including R3′, j, k, p, y, and z, are as defined or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed.

The invention provides novel compounds of formula I:that are opioid receptor ligands. The invention also provides pharmaceutical compositions comprising such compounds as well as methods for treating diseases associated with opioid receptor function by administering such compounds to a mammal in need of treatment. The invention also provides an improved method for isolating intermediate materials useful for obtaining compounds of formula I.

The present invention relates to a compound or combination for use in the treatment of skin wounds, skin aging, skin tumors and / or skin sensation conditions and / or for treatment to improve skin repair, wherein the compound or combination is:(a) a selective delta-opioid receptor (DOR) antagonist; or(b) a combination of a selective DOR antagonist and an opioid receptor agonist; or(c) a selective ligand for a sensory receptor; or(d) a combination of a selective DOR antagonist and a selective ligand for a sensory receptor; or(e) a combination of a selective DOR antagonist, an opioid receptor agonist and a selective ligand for a sensory receptor, andwherein the treatment comprises a step of administering an effective amount of the compound or combination to a subject in need of such treatment.

A dynorphin-A analog can be used for treatment, inhibition, and / or prevention of cocaine seeking behavior, and or the drug seeking behavior for a cocaine derivative or other structurally related substance. The dynorphin-A analog can be a cyclic dynorphin-A analog having sufficient systemic stability that crosses the blood-brain barrier so as to be active in the brain at kappa-opioid receptors (KOR) as an antagonist. Such activity at a KOR as an antagonist can be useful for cocaine management and reducing the desire, such as stress-related desires, for use of cocaine, crack, or the like. The KOR antagonist can be [N-benzylTyr1,cyclo(D-Asp5,Dap8)]Dyn A-(1-11) amide, salt thereof, prodrug thereof, and / or derivative thereof.

The invention provides novel 8-azabicyclo[3.2.1]octane compounds of formula (I) wherein R<1>, R<2>, R<3>, A, and G are defined in the specification, or a pharmaceutically-acceptable salt or solvate thereof, that are antagonists at the mu opioid receptor. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat conditions associated with mu opioid receptor activity, and processes and intermediates useful for preparing such compounds.

The present invention pertains to novel uses of endomorphine-1 peptide, analogs, and salts thereof for therapy of children, patients currently suffering from drug addiction, patients prone to opioid addiction, and patients with chemo-induced pain.

Disclosed are compounds of the formula (I) wherein R1, R2 R3 R4 R5, R6 and N are as disclosed herein. The compounds are useful for the treatment of chronic and acute pain.

Potent opioid receptor antagonists of formula (I) and their use as pharmacotherapies for treating depression, anxiety, schizophrenia, eating disorders, and addiction to cocaine, methamphetamine, nicotine, alcohol, and opiates are disclosed. More specifically, the disclosure provides potent and selective kappa opioid receptor antagonist compounds, pharmaceutical compositions of those compounds and uses of those compounds to ameliorate or treat addictions, eating disorders, etc.

The present invention relates a method of treating drug addiction in an individual by administering to the addicted individual a therapeutically effective amount of dextro-morphine capable of activating an opioid receptor. It is disclosed here that dextro-morphine is suitable for treating addiction to natural opiates, semi-synthetic opiates, fully synthetic opioids, and endogenous opioid peptides, as well as nicotine.

The invention discloses a new kappa-opiate receptor stimulant (quaternized U50488H) having protection function on ischemia heart. Quaternized U50488H is produced by reaction of kappa-opiate receptor stimulant U50488H and CH3I under the conditions of a polar solvent and a catalyst. Like U50488H, the quaternized product can obviously improve the function of ischemia / reperfused heart, obviously reduce the area of myocardial infarction, reduce leakage of myocardial enzyme and obviously reduce apoptosis number of myocardial cells. The new compound has the remarkable characteristic of avoiding passing blood brain barrier, thereby avoiding addiction and dependence caused by the situation that U50488H enters the brain tissue via blood circulation. The new kappa-opiate receptor stimulant having protection function on ischemia heart can be used for academic research and can also provide a possible new drug for clinical application to prevent and treat ischemic heart disease, thereby having good scientific research value and clinical application prospect.

The present invention refers to a new combination of sodium channel blockers, especially Tetrodotoxin, and their derivatives with opioid antagonists, especially naloxone, according medicinal products for human and / or animal therapeutics and their use for the treatment of a variety of diseases, especially pain, preferably neuropathic pain.