Copper Complexes Have Potent Analgesic Activity and They May Activate Opioid Receptors

Analgesia is commonly mediated through the mu or kappa opioid receptor agonism. Unfortunately, selective mu or kappa receptor agonists often cause harmful side effects. Recently, ligands exhibiting dual agonism to the opioid receptors, such as to mu and kappa, or to mu and delta, have been suggested to temper undesirable adverse effects while retaining analgesic activity. Herein we report an introduction of various 6,5-fused rings to C2 of the salvinorin scaffold via an ester linker. In vitro studies showed that some of these compounds have dual agonism on kappa and mu opioid receptors, while some have triple agonism on kappa, mu, and delta. In vivo studies on the lead dual kappa and mu opioid receptor agonist, compound 10, showed that it produced analgesic activity while avoiding anxiogenic effects in murine models, thus providing further strong evidence for the therapeutic advantages of dual opioid receptor agonists over selective opioid receptor agonists.

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Evaluation of Analgesic Activity ofPapaver libanoticumExtract in Mice: Involvement of Opioids Receptors

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/8935085 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 7

Author(s):

Mohamad Ali Hijazi ◽

Ahmed El-Mallah ◽

Maha Aboul-Ela ◽

Abdalla Ellakany

Keyword(s):

Opioid Receptors ◽

Analgesic Activity ◽

Time Course ◽

Ethanolic Extract ◽

Maximum Activity ◽

Tail Flick ◽

Endemic Plant ◽

Hot Plate ◽

The Central Nervous System ◽

Opioid Withdrawal Syndrome

Papaver libanoticumis an endemic plant to Lebanese region (family Papaveraceae) that has not been investigated before. The present study aimed to explore the analgesic activity of dried ethanolic extract ofPapaver libanoticum(PLE) using tail flick, hot plate, and acetic acid induced writhing models in mice. The involvement of opioid receptors in the analgesic mechanism was investigated using naloxone antagonism. Results demonstrated that PLE exhibited a potent dose dependent analgesic activity in all tested models for analgesia. The analgesic effect involved activation of opioid receptors in the central nervous system, where both spinal and supraspinal components might be involved. The time course for analgesia revealed maximum activity after three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioid receptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesia by PLE was double that of morphine in both tests. In conclusion, PLE proved to have opioid agonistic activity with a novel feature of slow and prolonged effect. The present study could add a potential tool in the armaments of opioid drugs as a natural potent analgesic and for treatment of opioid withdrawal syndrome.

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Evidence against the Participation of μ- and κ-Opioid Receptors in the Analgesic Activity of Ketorolac in Rats

Journal of Pharmacy and Pharmacology ◽

10.1111/j.2042-7158.1995.tb05841.x ◽

1995 ◽

Vol 47 (6) ◽

pp. 514-517 ◽

Cited By ~ 8

Author(s):

VINICIO GRANADOS-SOTO ◽

FRANCISCO J. FLORES-MURRIETA ◽

GILBERTO CASTAÑEDA-HERNÁNDEZ ◽

ENRIQUE HONG ◽

FRANCISCO J. LÓPEZ-MUÑOZ

Keyword(s):

Opioid Receptors ◽

Analgesic Activity

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Toxicity Assessment of Structurally Relevant Natural Products from Mexican Plants with Antinociceptive Activity

Journal of the Mexican Chemical Society ◽

10.29356/jmcs.v61i3.344 ◽

2017 ◽

Vol 61 (3) ◽

Cited By ~ 3

Author(s):

Karina Martinez-Mayorga ◽

Andrés F. Marmolejo-Valencia ◽

Fernando Cortes-Guzman ◽

Juan Carlos García-Ramos ◽

Eric Iván Sánchez-Flores ◽

...

Keyword(s):

Natural Products ◽

Acute Toxicity ◽

Opioid Receptors ◽

Analgesic Activity ◽

Structural Diversity ◽

Toxicity Assessment ◽

Bioactive Molecules ◽

Antinociceptive Activity ◽

Toxicological Profile ◽

The World

UNIIQUIM database contains molecules from Mexican plants, one of the richest sources of bioactive molecules in the world. Here, we describe the chemical and toxicological profile of molecules with analgesic activity from UNIIQUIM. Most of the compounds are likely to interact with opioid receptors. The predicted acute toxicity is low and none is predicted mutagenic. Given the structural diversity, and biological and toxicity profiles, these molecules represent a new avenue in the search of molecules with antinociceptive activity.

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Copper complexes of non-steroidal antiinflammatory agents: Analgesic activity and possible opioid receptor activation

Agents and Actions ◽

10.1007/bf01974933 ◽

1987 ◽

Vol 21 (1-2) ◽

pp. 130-144 ◽

Cited By ~ 46

Author(s):

Shigeru Okuyama ◽

Sanae Hashimoto ◽

Hironaka Aihara ◽

William M. Willingham ◽

John R. J. Sorenson

Keyword(s):

Opioid Receptor ◽

Analgesic Activity ◽

Copper Complexes ◽

Receptor Activation ◽

Antiinflammatory Agents

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Analgesic activity and selectivity of isothiocyanate derivatives of fentanyl analogs for opioid receptors

Life Sciences ◽

10.1016/s0024-3205(99)00404-x ◽

1999 ◽

Vol 65 (15) ◽

pp. 1589-1595 ◽

Cited By ~ 8

Author(s):

Chen Bi-Yi ◽

Jin Wen-Qiao ◽

Chen Jie ◽

Chen Xin-Jian ◽

Zhu You-Cheng ◽

...

Keyword(s):

Opioid Receptors ◽

Analgesic Activity ◽

Fentanyl Analogs ◽

Derivatives Of

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Himalayan Ficus palmata L. Fruit Extract Showed In Vivo Central and Peripheral Analgesic Activity Involving COX-2 and Mu Opioid Receptors

Plants ◽

10.3390/plants10081685 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1685

Author(s):

Devesh Tewari ◽

Pawan Gupta ◽

Sweta Bawari ◽

Archana N. Sah ◽

Davide Barreca ◽

...

Keyword(s):

Binding Affinity ◽

Opioid Receptors ◽

Analgesic Activity ◽

In Silico ◽

Mu Opioid Receptors ◽

Fruit Extract ◽

Mu Opioid ◽

Cox 2 ◽

Ficus Palmata

Analgesic drugs like morphine and non-steroidal anti-inflammatory drugs exhibit several harmful effects. Here, we show for the first time the analgesic activity of Ficus palmata L. fruit extract (FPFE) on different analgesic rat models along with the in silico studies of some of the main phytochemicals of this plant. We performed in vivo pain models, along with in silico docking studies against the active site of COX-2 protein and mu-opioid receptors. A significant (p < 0.05) analgesic effect of FPFE was observed, and it was found that rutin has good pose and score as compared to diclofenac and morphinan antagonist (X-ligand), and psoralen has binding affinity almost equal to diclofenac, but a lower binding affinity as compared to rutin. The results proved that F. palmata fruits have the potential to ameliorate painful conditions.

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6,5-Fused Ring, C2-Salvinorin Ester, Dual Kappa and Mu Opioid Receptor Agonists as Analgesics Devoid of Anxiogenic Effects

10.26434/chemrxiv.14204834 ◽

2021 ◽

Author(s):

Nicholas S. Akins ◽

Nisha Mishra ◽

Hannah M. Harris ◽

Narendar Dudhipala ◽

Seong Jong Kim ◽

...

Keyword(s):

Opioid Receptor ◽

Opioid Receptors ◽

Analgesic Activity ◽

Mu Opioid Receptor ◽

Kappa Opioid Receptor ◽

Mu Opioid ◽

Receptor Agonists ◽

Opioid Receptor Agonists

Analgesia is commonly mediated through the mu or kappa opioid receptor agonism. Unfortunately, selective mu or kappa receptor agonists often cause harmful side effects. Recently, ligands exhibiting dual agonism to the opioid receptors, such as to mu and kappa, or to mu and delta, have been suggested to temper undesirable adverse effects while retaining analgesic activity. Herein we report an introduction of various 6,5-fused rings to C2 of the salvinorin scaffold via an ester linker. In vitro studies showed that some of these compounds have dual agonism on kappa and mu opioid receptors, while some have triple agonism on kappa, mu, and delta. In vivo studies on the lead dual kappa and mu opioid receptor agonist, compound 10, showed that it produced analgesic activity while avoiding anxiogenic effects in murine models, thus providing further strong evidence for the therapeutic advantages of dual opioid receptor agonists over selective opioid receptor agonists.

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