JP-2022518788-A5 -

Dates

Publication Date

20221216

Application Date

20200128

Description

The criteria for determining effectiveness, used to assert effectiveness at the time of the final analysis, consist of the following two statements that must be true at the same time: 1. The posterior probability of Δ > 0 is greater than 90%; 2. The posterior probability of Δ > 0.20 is greater than 50%. The inventions described in the original claims of this application are listed below. [Invention 1] Use of mGluR5 antagonists such as compound (I) or (II) for the manufacture of drugs for the treatment of opioid analgesic tolerance associated with chronic opioid use in chronic pain. [Invention 2] The use of an mGluR5 antagonist such as compound (I) or (II) for the manufacture of a drug for the treatment of opioid analgesia associated with chronic opioid use in chronic pain, wherein the treatment reverses opioid analgesia. [Invention 3] Use of mGluR5 antagonists such as compound (I) or (II) for the manufacture of drugs for the treatment of reversing opioid analgesic tolerance associated with chronic opioid use in chronic pain. [Invention 4] Use of mGluR5 antagonists such as compound (I) or (II) for the manufacture of therapeutic drugs to reduce the risk of opioid-related overdose associated with chronic opioid use in chronic pain. [Invention 5] Use of mGluR5 antagonists such as compound (I) or (II) for the manufacture of drugs for the treatment of chronic pain to reverse opioid analgesic tolerance associated with chronic opioid use. [Invention 6] Use of mGluR5 antagonists such as compound (I) or (II) for the manufacture of drugs for the treatment of opioid analgesic tolerance to reduce the risk of opioid-related overdose associated with chronic opioid use in chronic pain. [Invention 7] Use of mGluR5 antagonists such as compound (I) or (II) for the manufacture of drugs for the treatment of reducing opioid consumption in chronic pain. [Invention 8] The use of an mGluR5 antagonist such as compound (I) or (II) for the manufacture of a drug for the treatment of reversing opioid analgesia associated with chronic opioid use in chronic pain, wherein the opioid dose administered to the patient [e.g., daily dose of opioids; e.g., more than 50 mg of oral morphine/day or daily analgesic dose of another opioid (i.e., milligram equivalent of morphine, MME/day)] is reduced (e.g., by 50% or more, such as 70% or more (e.g., 90% or more)) and the opioid analgesic effect (i.e., previously achieved by using higher opioid doses) is maintained. [Invention 9] The use of the mGluR5 antagonist for the manufacture of any one of Inventions 1 to 8, wherein the mGluR5 antagonist is administered to a patient taking an opioid dose of more than 50 mg of oral morphine/day or an equivalent daily analgesic dose of another opioid (i.e., milligram equivalents of morphine, MME/day), for example, a patient taking an opioid dose of 60 to 100 mg of oral morphine/day or an equivalent daily analgesic dose of another opioid. [Invention 10] Use of an mGluR5 antagonist for the manufacture of any one of Inventions 1 to 9, wherein chronic pain is associated with injury (e.g., wound, burn, or fracture) or disease (e.g., diabetes, multiple sclerosis, arthritis, autoimmune disease, or infection). [Invention 11] Use of an mGluR5 antagonist for the manufacture of any one of inventions 1 to 10, wherein the chronic pain is non-malignant chronic pain. [Invention 12] Use of an mGluR5 antagonist for the manufacture of the drug according to Invention 11, wherein non-malignant chronic pain is, for example, chronic back pain such as chronic low back pain, with or without a history of spinal surgery. [Invention 13] The use of the mGluR5 antagonist for the manufacture of any one of inventions 1 to 12, wherein the mGluR5 antagonist is administered to an elderly patient. [Invention 14] Use of an mGluR5 antagonist for the manufacture of any one of inventions 1 to 13, wherein the chronic pain is chronic postoperative neuropathic pain. [Invention 15] Use of an mGluR5 antagonist for the manufacture of a drug according to any one of inventions 1 to 14, wherein the mGluR5 antagonist is administered in the form of a pharmaceutical composition further comprising at least one pharmaceutically acceptable excipient. [Invention 16] The aforementioned mGluR5 antagonist is an antidepressant (e.g., tricyclic antidepressants such as amitriptyline, nortriptyline, doxepin, desipramine, imipramine, protriptyline, trimipramine, clomipramine, etc.), a serotonin-norepinephrine reuptake inhibitor (e.g., duloxetine, venlafaxine, desvenlafaxine, milnacipran, levomirnacipran), a serotonin reuptake inhibitor (e.g., fluoxetine, cetraline, paroxetine, Fluvoxamine, citalopram, escitalopram, bilazodone, vortioxetine), anticonvulsants (e.g., gabapentin, pregabalin, carbamazepine, valproic acid, phenytoin, lamotrigine, thiagabine, lacosamide, topiramate, levetiracetam, oxacarbazepine, zonisamide), nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., naproxen, ibuprofen, meloxicam, diclofenac, fenoprofen, f