Methods and compositions for modulating opioid withdrawal symptoms

A technology for withdrawal symptoms and compositions, applied in the field of screening compounds and compositions, can solve problems that plague chronic opiate users, ineffective clinical strategies, debilitating withdrawal syndrome, etc.

Active Publication Date: 2019-04-16
UTI LLP (CA)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, a major concern with discontinuing opiate pain therapy is the debilitating withdrawal syndrome that can plague chronic opiate users
Mechanisms involved in opiate withdrawal are poorly understood and limited clinical strategies available to treat withdrawal are ineffective

Method used

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  • Methods and compositions for modulating opioid withdrawal symptoms
  • Methods and compositions for modulating opioid withdrawal symptoms
  • Methods and compositions for modulating opioid withdrawal symptoms

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0104] The following methods and materials were used in the Examples disclosed in this application.

[0105] animal:

[0106] Adult male rats and mice (7-8 week old rats; 6-10 week old mice) were used. Mice and rats were housed on a 12 hr / 12 hr light / dark cycle with ad libitum access to food and water. All experiments were approved by the University of Calgary and Laval University Animal Care Committees and in accordance with the guidelines of the Canadian Humane Society.

[0107] Morphine Dose Paradigm and Nociceptive Behavior Model:

[0108] Morphine sulfate (PCCA) prepared in 0.9% sterile saline solution was injected intraperitoneally twice daily (8 am and 5 pm) into Sprague-Dawley rats (increasing doses from 10 to 45 mg / kg), Cx3cr1-cre::Pnx1 flx / flx , or Pnx1 flx / flx Mice (increasing doses from 7.5 to 50 mg / kg). Thermal nociceptive thresholds were assessed using the tail flick test (rats) and the tail immersion test (mice). For rats, an infrared heat stimulus (Ugo B...

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PUM

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Abstract

A method of screening a compound or a composition for use in modulating opioid withdrawal symptoms in a mammal. The method comprises the steps of: selecting a group of test animals; separating the group into two subgroups; inducing pannexin -1 activation or expression in both subgroups; dosing a first subgroup with a candidate compound; dosing a second subgroup with a placebo; measuring ATP released in spinal microglia of test animals from both subgroups; quantifying the difference in ATP released in spinal microglia of test animals from the first subgroup and the second subgroup; if the difference in the ATP released in the first subgroup and the ATP released in the second subgroup is greater than 25%, then formulating the candidate compound into a pharmaceutical composition. Also disclosed, pharmaceutical compositions for modulating opioid withdrawal symptoms in a subject comprising a pannexin- 1 inhibitor. Said inhibitor may be lOpanx peptide with amino acid sequence WRQAAFVDS Y, mefloquine or probenecid.

Description

technical field [0001] The present disclosure relates generally to the treatment of opioid or opioid-like drug-related substance use disorders. More particularly, the present disclosure relates to methods of screening compounds and compositions for the identification and selection of candidate therapeutic compounds and compositions effective in modulating opioid withdrawal symptoms. Background technique [0002] Opiates are among the most effective and widely prescribed drugs used to treat pain. However, a major concern with discontinuing opiate therapy for pain is the debilitating withdrawal syndrome that can plague chronic opiate users. Little is known about the mechanisms involved in opiate withdrawal, and the limited clinical strategies available to treat withdrawal are ineffective. Contents of the invention [0003] Embodiments of the present disclosure generally relate to the use of the pan-nexin-1 (Panx1 ) channel as a novel therapeutic target for the treatment of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17C12Q1/00G01N33/15G01N33/48C07K14/705A61K31/4709A61P25/36C07C311/16C07D401/06A61K31/196A61K38/08
CPCA61K31/4709A61P25/36G01N33/5058A61K38/08A61K31/195A61K49/0008A01K67/0276A01K67/0275A01K2217/075A01K2217/15A01K2227/105A01K2217/052A01K2217/206A61K9/0014A61K9/0019A61K9/0053A61K9/06A61K9/7023A61K31/473
Inventor T·特朗格N·博玛
Owner UTI LLP (CA)
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