Positive Allosteric Modulation of CB1 and CB2 Cannabinoid Receptors Enhances the Neuroprotective Activity of a Dual CB1R/CB2R Orthosteric Agonist
Preclinical studies highlighted that compounds targeting cannabinoid receptors could be useful for developing novel therapies against neurodegenerative disorders. However, the chronic use of orthosteric agonists alone has several disadvantages, limiting their usefulness as clinically relevant drugs....
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/10/12/333 |
| _version_ | 1797545404320972800 |
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| author | Beatrice Polini Chiara Cervetto Sara Carpi Simone Pelassa Francesca Gado Rebecca Ferrisi Simone Bertini Paola Nieri Manuela Marcoli Clementina Manera |
| author_facet | Beatrice Polini Chiara Cervetto Sara Carpi Simone Pelassa Francesca Gado Rebecca Ferrisi Simone Bertini Paola Nieri Manuela Marcoli Clementina Manera |
| author_sort | Beatrice Polini |
| collection | DOAJ |
| description | Preclinical studies highlighted that compounds targeting cannabinoid receptors could be useful for developing novel therapies against neurodegenerative disorders. However, the chronic use of orthosteric agonists alone has several disadvantages, limiting their usefulness as clinically relevant drugs. Positive allosteric modulators might represent a promising approach to achieve the potential therapeutic benefits of orthosteric agonists of cannabinoid receptors through increasing their activity and limiting their adverse effects. The aim of the present study was to show the effects of positive allosteric ligands of cannabinoid receptors on the activity of a potent dual orthosteric agonist for neuroinflammation and excitotoxic damage by excessive glutamate release. The results indicate that the combination of an orthosteric agonist with positive allosteric modulators could represent a promising therapeutic approach to the treatment of neurodegenerative disorders. |
| first_indexed | 2024-03-10T14:15:08Z |
| format | Article |
| id | doaj.art-f0f6420babd345b98003edb623f29996 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T14:15:08Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-f0f6420babd345b98003edb623f299962023-11-20T23:56:01ZengMDPI AGLife2075-17292020-12-01101233310.3390/life10120333Positive Allosteric Modulation of CB1 and CB2 Cannabinoid Receptors Enhances the Neuroprotective Activity of a Dual CB1R/CB2R Orthosteric AgonistBeatrice Polini0Chiara Cervetto1Sara Carpi2Simone Pelassa3Francesca Gado4Rebecca Ferrisi5Simone Bertini6Paola Nieri7Manuela Marcoli8Clementina Manera9Department of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, Section of Pharmacology and Toxicology, University of Genova, 16126 Genova, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, Section of Pharmacology and Toxicology, University of Genova, 16126 Genova, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyDepartment of Pharmacy, Section of Pharmacology and Toxicology, University of Genova, 16126 Genova, ItalyDepartment of Pharmacy, University of Pisa, 56126 Pisa, ItalyPreclinical studies highlighted that compounds targeting cannabinoid receptors could be useful for developing novel therapies against neurodegenerative disorders. However, the chronic use of orthosteric agonists alone has several disadvantages, limiting their usefulness as clinically relevant drugs. Positive allosteric modulators might represent a promising approach to achieve the potential therapeutic benefits of orthosteric agonists of cannabinoid receptors through increasing their activity and limiting their adverse effects. The aim of the present study was to show the effects of positive allosteric ligands of cannabinoid receptors on the activity of a potent dual orthosteric agonist for neuroinflammation and excitotoxic damage by excessive glutamate release. The results indicate that the combination of an orthosteric agonist with positive allosteric modulators could represent a promising therapeutic approach to the treatment of neurodegenerative disorders.https://www.mdpi.com/2075-1729/10/12/333endocannabinoids systemcannabinoid receptor type 2cannabinoid receptor type 1positive allosteric modulatormicroglial cellglutamate release |
| spellingShingle | Beatrice Polini Chiara Cervetto Sara Carpi Simone Pelassa Francesca Gado Rebecca Ferrisi Simone Bertini Paola Nieri Manuela Marcoli Clementina Manera Positive Allosteric Modulation of CB1 and CB2 Cannabinoid Receptors Enhances the Neuroprotective Activity of a Dual CB1R/CB2R Orthosteric Agonist Life endocannabinoids system cannabinoid receptor type 2 cannabinoid receptor type 1 positive allosteric modulator microglial cell glutamate release |
| title | Positive Allosteric Modulation of CB1 and CB2 Cannabinoid Receptors Enhances the Neuroprotective Activity of a Dual CB1R/CB2R Orthosteric Agonist |
| title_full | Positive Allosteric Modulation of CB1 and CB2 Cannabinoid Receptors Enhances the Neuroprotective Activity of a Dual CB1R/CB2R Orthosteric Agonist |
| title_fullStr | Positive Allosteric Modulation of CB1 and CB2 Cannabinoid Receptors Enhances the Neuroprotective Activity of a Dual CB1R/CB2R Orthosteric Agonist |
| title_full_unstemmed | Positive Allosteric Modulation of CB1 and CB2 Cannabinoid Receptors Enhances the Neuroprotective Activity of a Dual CB1R/CB2R Orthosteric Agonist |
| title_short | Positive Allosteric Modulation of CB1 and CB2 Cannabinoid Receptors Enhances the Neuroprotective Activity of a Dual CB1R/CB2R Orthosteric Agonist |
| title_sort | positive allosteric modulation of cb1 and cb2 cannabinoid receptors enhances the neuroprotective activity of a dual cb1r cb2r orthosteric agonist |
| topic | endocannabinoids system cannabinoid receptor type 2 cannabinoid receptor type 1 positive allosteric modulator microglial cell glutamate release |
| url | https://www.mdpi.com/2075-1729/10/12/333 |
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