Novel endomorphin analogues CEMR-1 and CEMR-2 produce potent and long-lasting antinociception with a favourable side effect profile at the spinal level
© 2023 British Pharmacological Society..
BACKGROUND AND PURPOSE: Endomorphins have shown great promise as pharmaceutics for the treatment of pain. We have previously confirmed that novel endomorphin analogues CEMR-1 and CEMR-2 behaved as potent μ agonists and displayed potent antinociceptive activities at the supraspinal and peripheral levels. The present study was undertaken to evaluate the antinociceptive properties of CEMR-1 and CEMR-2 following intrathecal (i.t.) administration. Furthermore, their antinociceptive tolerance and opioid-like side effects were also determined.
EXPERIMENTAL APPROACH: The spinal antinociceptive effects of CEMR-1 and CEMR-2 were determined in a series of pain models, including acute radiant heat paw withdrawal test, spared nerve injury-induced neuropathic pain, complete Freund's adjuvant-induced inflammatory pain, visceral pain and formalin pain. Antinociceptive tolerance was evaluated in radiant heat paw withdrawal test.
KEY RESULTS: Spinal administration of CEMR-1 and CEMR-2 produced potent and prolonged antinociceptive effects in acute pain. CEMR-1 and CEMR-2 may produce their antinociception through distinct μ receptor subtypes. These two analogues also exhibited significant analgesic activities in neuropathic, inflammatory, visceral and formalin pain at the spinal level. It is noteworthy that CEMR-1 showed non-tolerance-forming analgesic properties, while CEMR-2 exhibited substantially reduced antinociceptive tolerance. Furthermore, both analogues displayed no or reduced side effects on conditioned place preference response, physical dependence, locomotor activity and gastrointestinal transit.
CONCLUSIONS AND IMPLICATIONS: The present investigation demonstrated that CEMR-1 and CEMR-2 displayed potent and long-lasting antinociception with a favourable side effect profile at the spinal level. Therefore, CEMR-1 and CEMR-2 might serve as promising analgesic compounds with minimal opioid-like side effects.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:181 |
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| Enthalten in: |
British journal of pharmacology - 181(2024), 8 vom: 21. März, Seite 1268-1289 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Yu-Zhe [VerfasserIn] |
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| Links: |
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| Themen: |
1HG84L3525 |
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| Anmerkungen: |
Date Completed 19.03.2024 Date Revised 19.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/bph.16287 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364821078 |
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| 100 | 1 | |a Zhang, Yu-Zhe |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Novel endomorphin analogues CEMR-1 and CEMR-2 produce potent and long-lasting antinociception with a favourable side effect profile at the spinal level |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 19.03.2024 | ||
| 500 | |a Date Revised 19.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 British Pharmacological Society. | ||
| 520 | |a BACKGROUND AND PURPOSE: Endomorphins have shown great promise as pharmaceutics for the treatment of pain. We have previously confirmed that novel endomorphin analogues CEMR-1 and CEMR-2 behaved as potent μ agonists and displayed potent antinociceptive activities at the supraspinal and peripheral levels. The present study was undertaken to evaluate the antinociceptive properties of CEMR-1 and CEMR-2 following intrathecal (i.t.) administration. Furthermore, their antinociceptive tolerance and opioid-like side effects were also determined | ||
| 520 | |a EXPERIMENTAL APPROACH: The spinal antinociceptive effects of CEMR-1 and CEMR-2 were determined in a series of pain models, including acute radiant heat paw withdrawal test, spared nerve injury-induced neuropathic pain, complete Freund's adjuvant-induced inflammatory pain, visceral pain and formalin pain. Antinociceptive tolerance was evaluated in radiant heat paw withdrawal test | ||
| 520 | |a KEY RESULTS: Spinal administration of CEMR-1 and CEMR-2 produced potent and prolonged antinociceptive effects in acute pain. CEMR-1 and CEMR-2 may produce their antinociception through distinct μ receptor subtypes. These two analogues also exhibited significant analgesic activities in neuropathic, inflammatory, visceral and formalin pain at the spinal level. It is noteworthy that CEMR-1 showed non-tolerance-forming analgesic properties, while CEMR-2 exhibited substantially reduced antinociceptive tolerance. Furthermore, both analogues displayed no or reduced side effects on conditioned place preference response, physical dependence, locomotor activity and gastrointestinal transit | ||
| 520 | |a CONCLUSIONS AND IMPLICATIONS: The present investigation demonstrated that CEMR-1 and CEMR-2 displayed potent and long-lasting antinociception with a favourable side effect profile at the spinal level. Therefore, CEMR-1 and CEMR-2 might serve as promising analgesic compounds with minimal opioid-like side effects | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CEMR-1 and CEMR-2 | |
| 650 | 4 | |a antinociception | |
| 650 | 4 | |a i.t. administration | |
| 650 | 4 | |a opioid receptors | |
| 650 | 4 | |a side effects | |
| 650 | 4 | |a tolerance | |
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| 650 | 7 | |a Analgesics |2 NLM | |
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| 650 | 7 | |a 1HG84L3525 |2 NLM | |
| 700 | 1 | |a Wang, Si-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Xue-Ci |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiao-Han |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiao-Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Meng-Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Ting-Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Feng-Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chang-Lin |e verfasserin |4 aut | |
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