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Methods of treating hyperalgesia

A technology for hyperalgesia and subjects, which can be used in pharmaceutical formulations, medical preparations containing active ingredients, drug combinations, etc., and can solve problems such as hyperalgesia in patients

Pending Publication Date: 2018-08-03
特维娜SPV2有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Additionally, patients administered morphine and similar non-biasing ligands may suffer from hyperalgesia

Method used

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  • Methods of treating hyperalgesia
  • Methods of treating hyperalgesia
  • Methods of treating hyperalgesia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0244] Example 1: Biasing Ligands Do Not Induce Hyperalgesia Compounds were tested for their potential to induce hyperalgesia in a mouse model of opioid-induced hyperalgesia. In this test, mice (n=8 / group) were injected subcutaneously with vehicle or mu opioid agonist twice daily for 4 days. Measurements of mechanical hyperalgesia were obtained using repeated stimulation with a single von Frey monofilament (0.4 g) on ​​each of the four drug treatment days. On the fifth day, the animals were tested again without additional drug treatment. For testing, a monofilament is applied to the hind paw for approximately 1-2 seconds. If there is a withdrawn response, it is recorded as a positive response. Each mouse was repeated ten times. The final measurement for each mouse was the percentage non-response to the stimulus out of ten trials. The result is as figure 1 shown. Compound A is Compound 265 and Compound B is Compound 54.

[0245] Graph shows the percentage of non-response...

Embodiment 2

[0247] Example 2: Biased Ligands Reverse Opioid-Induced Hyperalgesia Compounds were tested for their potential to reverse opioid-induced hyperalgesia in a mouse model of opioid-induced hyperalgesia. In this test, mice (n=8 / group) were injected subcutaneously with vehicle or reference mu opioid agonist twice daily for 4 days. Measurements of mechanical hyperalgesia were obtained using repeated stimulation with a single von Frey monofilament (0.4 g) on ​​each of the four drug treatment days. Animals already receiving the reference mu opioid agonist were switched to compound B after behavioral testing on day five. Subcutaneous injections were continued twice daily until day 12. Behavioral assessments of mechanical allodynia were performed on days 5, 6, 7, 8, 10, and 12. For testing, a monofilament is applied to the hind paw for approximately 1-2 seconds. If there is a withdrawn response, it is recorded as a positive response. Each mouse was repeated ten times. The final meas...

Embodiment 3

[0248] Example 3: Human subjects prescribed morphine exhibit symptoms of opioid-induced hyperalgesia. Subjects discontinued morphine and administered Compound 140 or Compound 265. Treat and reduce opioid-induced hyperalgesia in a subject. Subjects continued to take Compound 140 or Compound 265 and did not suffer from hyperalgesia while maintaining pain relief.

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PUM

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Abstract

This invention describes compounds and methods that can be used to treat, reverse, or avoid hyperalgesia.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application No. 62 / 267,144, filed December 14, 2015, the entire disclosure of which is incorporated herein by reference. This application is also related to U.S. Nonprovisional Application No. 13 / 428,849, filed March 23, 2012, Provisional Application No. 61 / 596,808, filed February 9, 2012, and U.S. Provisional Application No. 61 / 596,808, filed March 23, 2011 Application No. 61 / 466,809, the entire contents of each of which are incorporated herein by reference. technical field [0003] This application relates to a family of compounds useful as opioid receptor ligands and methods of using these compounds to treat or reverse hyperalgesia, treat or reverse induced hyperalgesia, reduce nociceptive sensitization, and the like. Background technique [0004] Opioid receptors (ORs) mediate the effects of morphine and morphine-like opioids, including most clinical analgesics. ...

Claims

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Application Information

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IPC IPC(8): A61K31/4433A61K31/497A61P1/10C07D405/04
CPCA61K45/06A61K31/444A61K31/4468A61K31/485A61K31/35A61K31/4433A61K31/4436C07D409/12A61P1/10A61P25/00A61P25/04A61P43/00A61K2300/00C07D409/14
Inventor 康拉德·考恩迈克尔·科布利什迈克尔·W·拉克
Owner 特维娜SPV2有限责任公司
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