141 results about "Opioid receptor" patented technology

The present invention provides kappa opioid receptor peptide agonists, methods for preparing these compounds, compositions comprising these kappa opioid receptor peptide agonists, and methods of using the kappa opioid receptor peptide agonists to treat pain or other conditions.

The invention relates to a drug-loaded bone filling material, a preparation method thereof and application of the drug-loaded bone filling material in inhibition of relapse of opioid drugs. The drug-loaded bone filling material is prepared from the following raw materials: powder and curing liquid, the powder comprises a mixture of an opioid receptor antagonist and inorganic calcium salt; in the powder, the mass ratio of the opioid receptor antagonist to the inorganic calcium salt is 4-20%. After a performance test, the drug-loaded bone filling material has the advantages of proper coagulation time, good compressive strength and better drug sustained release characteristic, on one hand, artificial bones capable of promoting osteoblast differentiation can be filled in a bone defect area, and on the other hand, side effects caused by opioid drugs can be relieved, and symptoms can be relieved; meanwhile, for relieving opioid addicts, long-time drug action can be maintained, relapse can be prevented or reduced, and the pharmaceutical composition has great application potential in promoting osteoblast differentiation or inhibiting relapse of opioid drugs.

The invention relates to particular substituted heterocycle fused gamma-carbolines, their prodrugs, in free, solid, pharmaceutically acceptable salt and / or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving the 5-HT2A receptor, the serotonin transporter (SERT), pathways involving the dopamine D1 and D2 receptor signaling system, and / or the μ-opioid receptor.

The invention relates to the technical field of biology and biology, in particular to a screening method of thermostable mutation sites of a G protein coupled receptor and application of the thermostable mutation sites of the G protein coupled receptor, and the screening method comprises the following steps: S1, replacing a third intracellular ring segment in a wild type G protein coupled receptor with a third intracellular ring sequence of a kappa opioid receptor; marking a SmBiT peptide fragment label on the wild type G protein coupled receptor; s2, mutating a wild type G protein coupled receptor according to a mutation site in the G protein coupled receptor mutant to be detected; s3, incubating the G protein coupled receptor modified in the step S2 at different temperatures to obtain modified G protein coupled receptor samples treated at different temperatures; s4, carrying out mixed incubation on the modified G protein coupled receptor samples treated at different temperatures and a nano antibody-LgBiT compound, then adding luciferase to act as a substrate, and detecting; the method is high in screening efficiency, low in cost and short in time.

Disclosed herein is a solid Form A of 1-(6-ethyl-8-fluoro-4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)quinolin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidin-4-amine hydrochloride exhibiting at least X-ray lines (in degrees 2θ ± 0.2) at 4.30, 8.59, 12.88, 18.82 and 21.34 in a powder diffraction pattern when measured using Cu Kα radiation. The solid Form A is an antagonist of the kappa-opioid receptor (KOR) and is useful for treating conditions that benefit from the same. Compositions comprising the solid Form A, as well as related methods of use are also disclosed.

Disclosed are a peptide amide compound composition, a preparation method therefor and medical use thereof. Specifically, the composition contains a compound of formula (I) and pH regulators, and the pH of the solution thereof is 3-5.5. The composition is stable and requires few excipients, and is stable in clinical use. The composition is used for treating or preventing a disease or condition associated with kappa opioid receptors

The invention relates to particular prodrugs of substituted heterocycle fused gamma-carbolines, in free, solid, pharmaceutically acceptable salt and / or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving the 5-HT2A receptor, the serotonin transporter (SERT), pathways involving the dopamine D1 and D2 receptor signaling system, and / or the μ-opioid receptor.

Methods and compositions are provided for treating individuals exhibiting opioid withdrawal symptoms with opioid, benzodiazepine and other drugs of abuse by administering an opioid receptor antagonist agent together with a respiratory stimulant to reverse the effects of opioid withdrawal symptoms, including respiratory depression, sedation, and hypotension. Methods and compositions are also provided for treating stimulant overdose with a benzodiazepine and beta-adrenergic blocking agent. Methods and compositions are also provided for treating concurrent stimulant and opioid overdose comprising administering to a patient in need thereof a benzodiazepine and an opioid antagonist. Methods and compositions are also provided for treating individuals exhibiting opioid withdrawal symptoms or prophy tactically treating individuals for opioid withdrawal symptoms from opioid, benzodiazepine and other drugs of abuse by administering an opioid receptor antagonist agent together with a respiratory stimulant to reverse the effects of withdrawal, including respiratory depression, sedation, and hypotension.

The invention relates to particular substituted heterocycle fused gamma-carbolines, in free, solid, pharmaceutically acceptable salt and / or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving the 5-HT2A receptor, the serotonin transporter (SERT), pathways involving the dopamine D1 and D2 receptor signaling system, and / or the μ-opioid receptor.

A series of non-peptide mu opioid receptor (MOR) selective modulators is provided. The compounds have the general formula (I) where R is (II) and where one of a, b, c, d, e or f is the point of attachment of indole ring R to the epoxymorphinan skeleton; at least one of the atoms at positions a, b, c, d, e and f is N; the remaining atoms at positions at a, b, c, d, e and f are CH; and * is a chiral carbon. The compounds are generally MOR antagonists and are used to treat disorders related to opioid receptor functions such as opioid addiction and opioid overdose, for the treatment of neurological diseases and for the treatment of pain, without causing constipation.

Provided herein are compositions and methods of using a Mu opioid receptor (MOR) antagonist (e.g. axelopran) alone or in combination with checkpoint inhibitor (such as e.g. an inhibitor of the PD-1 / PD-L1 pathway (e.g. an antibody such e.g. pem-brolizumab)) and / or an inhibitor of VEGF (e.g. bevacizumab) for reducing angiogenesis or treating cancer. Also provided herein are kits containing a MOR antagonist (e.g. axelopran) alone or in combination with checkpoint inhibitor and / or an inhibitor of VEGF for reducing angiogenesis or treating cancer.

The present application provides a pharmaceutical composition containing a polypeptide compound and a preparation method thereof, wherein the polypeptide compound has peripheral κ opioid receptor agonist activity. Therefore, the present application also relates to the use of the pharmaceutical composition in the preparation of a drug for preventing or treating diseases associated with κ opioid receptors.

Problem The purpose of the present invention is to provide a novel method for prevention and / or treatment of opioid tolerance or opioid dependence. Specifically, the purpose of the present invention is to develop peptide-based blockers to block MOR-DOR and KOR-DOR heterodimerization. In addition, the purpose of the present invention is to develop homodimer blockers for MOR, DOR, and KOR which modulate their downstream signaling without affecting their internalization. Solution The present invention is a prophylactic and / or therapeutic agent for the prevention and / or treatment of opioid tolerance or opioid dependence comprising the peptide which inhibits the dimer formation of the opioid receptor, wherein the above opioid receptor dimer is a heterodimer or a homodimer formed from one or two opioid receptors selected from the group consisting of the μ type (MOR), the κ type (KOR), and the δ type (DOR).

The present application discloses a compound of formula (I), compositions comprising said compound, and a method of using said compound as a cannabinoid receptor ligand in the treatment or prevention of diseases associated with a cannabinoid receptor, such as, CB1, CB2, 5HT1A, 5HT2A, GPR18, GPR119, TRPV1, TPRV2, PPARγ or a μ-opioid receptor.

The invention provides novel ligands of Kappa (κ) opioid receptors, such as can be used to modulate a Kappa opioid receptor. Methods of synthesis and methods of use are also provided. Compounds of the invention can be used therapeutically in the treatment of dissociative disorders or pain, or to provide neuroprotection, or to induce diuresis, or to modulate the immune system, or for treatment of one or more of an affective disorders comprising depression or stress / anxiety; an addictive disorder; alcoholism, epilepsy; a cognition deficiency; schizophrenia; Alzheimer's disease; or pain.

The present disclosure relates to compositions that upregulate the production of one or more sequences of micro-interfering ribonucleic acid (miRNA). The sequences of miRNA may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule, and the miRNA may cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is an opioid receptor. In some embodiments of the present disclosure, the target biomolecule is one or more of the mu opioid receptor, the delta opioid receptor, the kappa opioid receptor and the nociceptin opioid receptor.

Disclosed herein are compounds of Formula (I), and pharmaceutically acceptable salts thereof, that are negative allosteric modulators of the p-opioid receptor (MOR). Also disclosed are methods of inhibiting MOR as well as treating opioid overdose.

The present invention provides a pharmaceutical composition for treating or preventing anhedonia, said composition comprising, as an active ingredient, a selective δ opioid receptor agonist, wherein preferably, the selective δ opioid receptor agonist further has a κ opioid receptor antagonist action and a μ opioid receptor antagonist action.

Provided is a composition comprising Chlamydomonas reinhardtii or an extract of Chlamydomonas reinhardtii, the Chlamydomonas reinhardtii or the extract of Chlamydomonas reinhardtii comprising an agonist of an opioid receptor.

Disclosed herein is a solid Form A of 1-(6-ethyl-8-fluoro-4-methyl-3-(3-methyl-1,2,4-oxadiazol-5-yl)quinolin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)piperidin-4-amine hydrochloride exhibiting at least X-ray lines (in degrees 2θ±0.2) at 4.30, 8.59, 12.88, 18.82 and 21.34 in a powder diffraction pattern when measured using Cu Kα radiation. The solid Form A is an antagonist of the kappa-opioid receptor (KOR) and is useful for treating conditions that benefit from the same. Compositions comprising the solid Form A, as well as related methods of use are also disclosed.

A series of non-peptide opioid receptor modulators having the general formula: (I) is provided. In the formula: R = (II) * is a chiral carbon; M is a saturated or unsaturated, branched or unbranched, substituted or unsubstituted alkyl chain from 0-10 atoms in length; X1, X2, X3, X4, or X5 are independently, C, N, O, or S; and R is attached to M by any of X1, X2, X3, X4, or X5. The compounds are used to treat disorders related to opioid receptor functions such as opioid addiction, opioid overdose, pain and constipation caused by opioid use.

The present invention relates to a pharmaceutical composition for treating drug addiction comprising opioid receptor nanodiscs and to a method for preparing opioid receptor nanodiscs. Specifically, the opioid receptor nanodiscs, according to the present invention, inhibit the interaction between an opioid receptor and an opioid-based drug without exhibiting toxicity in the body, are delivered to the brain when administered into the body, and significantly restore the delay in a hot-plate response caused by opioid-based drug addiction, thereby being usefully applicable to treatment of opioid-based drug addiction.

The present invention provides a compound having the structure wherein A is a ring structure, with or without substitution; X1 is C or N; X2 is N, O, or S; Y1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 2 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y3 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 4 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y5 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); a and P are each present or absent and when present each is a bond.

Provided herein are opioid receptor modulators and pharmaceutical compositions comprising said compounds.

The present invention provides methods for modulating opioid receptor mediated analgesic effect, e.g., promoting or enhancing analgesia in subjects in need of pain relief. Also provided in the invention are methods for ameliorating or suppressing withdrawal symptoms in subjects with chronic opioid use. These methods of the invention entail administering to the subjects in need of treatment a therapeutically effective amount of a GPR139 antagonist compound. The invention further provides methods for identifying novel compounds that can be useful for modulating opioid receptor mediated analgesic effect.

The invention discloses aza-2-ketone derivatives, a synthesis method thereof and application of the aza-2-ketone derivatives in preparation of drugs. According to the invention, an alpha-carbonyl acyl silane compound is taken as a raw material, and under illumination, the alpha-carbonyl acyl silane compound and a vinyl aziridine compound are subjected to [5 + 2] cycloaddition reaction, so that a series of aza-2-ketone derivatives with different structures are simply and efficiently synthesized. The aza-2-ketone derivative disclosed by the invention can be further converted into medicine molecules such as kappa-opioid receptor selective agonist molecules and the like. The method has the advantages of easily available raw materials, simple operation, mild reaction conditions, and diversity of functional groups.

The invention relates to a tetrahydrothebaine derivative as well as a preparation method and application thereof, in particular to a 7alpha-(4 '-substituted amidophenyl)-6alpha, 14alpha-endo-ethylidene (alkenyl)-tetrahydrothebaine derivative as shown in a general formula (I) or pharmaceutically acceptable salts thereof and a preparation method of the 7alpha-(4'-substituted amidophenyl)-6alpha, 14alpha-endo-ethylidene (alkenyl)-tetrahydrothebaine derivative. And to the use of such derivatives in the preparation of medicaments for the treatment and / or prevention of pain, irritable bowel syndrome, pruritus, addiction, depression. The derivative disclosed by the invention has a remarkable improvement effect in the aspects of agonistic activity of the kappa opioid receptor, subtype selectivity of the kappa opioid receptor and central safety.

The subject matter disclosed herein relates generally to cancer therapy and to anticancer compounds and imaging agents. More specifically, the subject matter disclosed herein relates to agents that target DOR and their use in the treatment of cancer.

A composition and method for treatment of opioid use disorder (OUD) is provided by expressing a novel mu receptor mutant, LAMuOR (Low Affinity Mu Opioid Receptor), with reduced binding affinity for opioids such that it is activated only by the high concentration of exogenous opioids encountered in OUD but not by the low concentrations of endogenous opioids that occur physiologically. When expressed in specific brain circuits, these low-affinity mu opioid receptors can suppress reward-related neuronal activity specifically in the presence of opioids of abuse, thereby reducing abuse potential.

Disclosed herein are kappa opioid receptor (KOR) antagonist compounds of formula (I) and formula (II) and their pharmaceutically acceptable salts, as well as pharmaceutical compositions thereof. The compounds are useful in methods for treating a variety of diseases and disorders for which KOR antagonism is indicated, including substance abuse disorders, depression, anxiety, and other psychiatric conditions. TIFF2026506965000204.tif34128