Positive Allosteric Modulation of CB1 and CB2 Cannabinoid Receptors Enhances the Neuroprotective Activity of a Dual CB1R/CB2R Orthosteric Agonist.

cannabinoid receptor type 1 cannabinoid receptor type 2 endocannabinoids system glutamate release microglial cell positive allosteric modulator

Journal

Life (Basel, Switzerland)
ISSN: 2075-1729
Titre abrégé: Life (Basel)
Pays: Switzerland
ID NLM: 101580444

Informations de publication

Date de publication:
08 Dec 2020
Historique:
received: 04 11 2020
revised: 04 12 2020
accepted: 06 12 2020
entrez: 11 12 2020
pubmed: 12 12 2020
medline: 12 12 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33302569
pii: life10120333
doi: 10.3390/life10120333
pmc: PMC7763181
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla
ID : NET-2016-02363765 ; cod 2017/R/16 to CM

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Auteurs

Beatrice Polini (B)

Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.

Chiara Cervetto (C)

Department of Pharmacy, Section of Pharmacology and Toxicology, University of Genova, 16126 Genova, Italy.

Sara Carpi (S)

Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.

Simone Pelassa (S)

Department of Pharmacy, Section of Pharmacology and Toxicology, University of Genova, 16126 Genova, Italy.

Francesca Gado (F)

Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.

Rebecca Ferrisi (R)

Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.

Simone Bertini (S)

Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.

Paola Nieri (P)

Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.

Manuela Marcoli (M)

Department of Pharmacy, Section of Pharmacology and Toxicology, University of Genova, 16126 Genova, Italy.

Clementina Manera (C)

Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.

Classifications MeSH