Albert Einstein College of Medicine

Other

United Biomedical, Inc.

Ke-fei Shen

Stanley M Crain

Gerald M Fleischner

Chang Yi Wang

John A Kessler

Stuart C Apfel

Barry M Sherman

Nadav Friedmann

Xiong-qi Gong

Bo-yi Qin

Mao Huang

Mary Remien

Remi Barbier

This invention relates to a method for selectively enhancing the analgesic potency of a bimodally-acting opioid agonist such as morphine and simultaneously attenuating anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects associated with the administration of the bimodally-acting opioid agonist. The method of the present invention comprises administering to a subject an analgesic or sub-analgesic amount of a bimodally-acting opioid agonist such as morphine and an amount of an excitatory opioid receptor antagonist such as naltrexone or nalmefene effective to enhance the analgesic potency of the bimodally-acting opioid agonist and attenuate the anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects of the bimodally-acting opioid agonist.

Method of simultaneously enhancing analgesic potency and attenuating dependence liability caused by morphine and other bimodally-acting opioid agonists

The invention generally relates to compositions and methods with tramadol and an opioid antagonist to enhance analgesic potency and/or attenuate one or more adverse effects of tramadol, including adverse side effect(s) in humans such as nausea, vomiting, dizziness, headache, sedation (somnolence) or pruritis. This invention relates to compositions and methods for selectively enhancing the analgesic potency of tramadol and simultaneously attenuating anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects associated with the administration of tramadol. The methods of the present invention comprise administering to a subject an analgesic or subanalgesic amount of tramadol and an amount of excitatory opioid receptor antagonist such as naltrexone or nalmefene effective to enhance the analgesic potency of tramadol and attenuate the anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects of tramadol.

Compositions and methods for enhancing analgesic potency of tramadol and attenuating its adverse side effects

This invention relates to a method for treating a subject with irritable bowel syndrome (&ldquo;IBS&rdquo;) which comprises long-term administration of an opioid receptor antagonist at an appropriately low dose which will selectively antagonize excitatory opioid receptor functions, but not inhibitory opioid receptor functions, in myenteric neurons in the intestinal tract as well as in neurons of the central nervous system (&ldquo;CNS&rdquo;). The administration of the opioid receptor antagonist at a low dose enhances the potency of the inhibitory effects of endogenous opioid peptides present in the intestinal tract and the CNS, thereby reducing abdominal pain and stool frequency resulting from abnormally supersensitized excitatory opioid receptor functions. The invention also relates to a composition for treating a subject with IBS, which comprises an effective dose of an opioid receptor antagonist, and a pharmaceutically acceptable carrier.

Method and composition for treating irritable bowel syndrome using low doses of opioid receptor antagonists

Method and simultaneously enhancing analgesic potency and attenuating dependence liability caused by morphine and other bimodally-acting opioid agonists

This invention relates to a method for eating a subject with irritable bowel syndrome (&ldquo;IBS&rdquo;) which comprises long-term administration of an opioid receptor antagonist at an appropriately low dose which will selectively antagonize excitatory opioid receptor functions, but not inhibitory opioid receptor functions, in myenteric neurons in the intestinal tract as well as in neurons of the central nervous system (&ldquo;CNS&rdquo;). The administration of the opioid receptor antagonist at a low dose enhances the potency of the inhibitory effects of endogenous opioid peptides present in the intestinal tract and the CNS, thereby reducing abdominal pain and stool frequency resulting from abnormally supersensitized excitatory opioid receptor functions. The invention also relates to a composition for treating a subject with IBS, which comprises an effective dose of an opioid receptor antagonist, and a pharmaceutically acceptable carrier.

Method of simultaneously enhancing analgesic potency and attenuating

The present invention relates to a method of using a bioassay consisting of an electrophysiological method and a cell culture system of dorsal-root ganglion (DRG) neurons to screen and identify opioids with a high potential for use as 'low- or non-addictive' analgesics. Another aspect of the invention relates to a specific group of opioid alkaloids and analogues thereof identified by the bioassay of the invention for the unique ability to activate only inhibitory, but not excitatory, opioid receptor function, for use as low- or non-addictive analgesics. Another aspect of the invention relates to the specific use of etorphine or dihydroetorphine of the opioid alkaloid family as low- or non-addictive analgesics and for the treatment of opioid addiction.

Method for identification of low/non-addictive opioid analgesics and the

This invention relates to a method of preventing hyperalgesia and other undesirable side-effects associated with the administration of growth factor, including nerve growth factor, utilizing an antagonist capable of inactivating excitatory opioid receptor-mediated functions on neurons in the nociceptive pathway. In addition, this invention relates to a composition comprising a growth factor and an antagonist capable of inactivating excitatory opioid receptor-mediated functions on neurons in the nociceptive pathway.

Use of excitatory opioid receptor antagonists to prevent growth

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.

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 inhibitory 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 caused by said bimodally-acting opioid agonists. This invention further relates to a method of detoxifying and treating opiate addicts utilizing said opioid receptor antagonists, as well as to a composition comprising an excitatory opioid receptor antagonist of the invention and a bimodally-acting opioid agonist.

Growing community of inventors

Flushing, NY, United States of America

Ke-fei Shen