Topics

Do toxic synthetic cannabinoid receptor agonists have signature in vitro activity profiles? A case study of AMB-FUBINACA.

08:00 EDT 12th September 2019 | BioPortfolio

Summary of "Do toxic synthetic cannabinoid receptor agonists have signature in vitro activity profiles? A case study of AMB-FUBINACA."

Recreational consumption of synthetic cannabinoid receptor agonists (SCRAs) is a growing crisis in public health, in many parts of the world. AMB-FUBINACA is a member of this class of drugs, and is responsible for a large proportion of SCRA-related toxicity both in New Zealand and internationally. Strikingly, little is currently known about the mechanisms by which SCRAs exert toxic effects - nor whether their activity through the CB1 cannabinoid receptor (the mediator of cannabinoid-related psychoactivity) are sufficient to explain clinical observations. The current study therefore set out to perform a basic molecular pharmacology characterization of AMB-FUBINACA (in comparison to traditional research cannabinoids CP55,940, WIN55,212-2, and Δ9-THC) in fundamental pathways of receptor activity, including cAMP inhibition, pERK activation, ability to drive CB1 internalization, and ability to induce translocation of β-arrestins 1 and -2. Activity pathways were then compared by Operational analysis, to indicate whether AMB-FUBINACA may be a biased ligand. Results revealed that AMB-FUBINACA is highly efficacious and potent in all pathways assayed. However, surprisingly, bias analysis suggested that Δ9-THC, not AMB-FUBINACA, may be a biased ligand - being less active in both arrestin pathways than predicted by the activity of the other ligands tested. These data may help predict molecular characteristics of SCRAs. However, more research is required to determine whether these molecular effects manifest in toxicity at tissue/system level.

Affiliation

Journal Details

This article was published in the following journal.

Name: ACS chemical neuroscience
ISSN: 1948-7193
Pages:

Links

DeepDyve research library

PubMed Articles [15308 Associated PubMed Articles listed on BioPortfolio]

Insights into biased signaling at cannabinoid receptors: synthetic cannabinoid receptor agonists.

Cannabinoid receptors type 1 (CB) and type 2 (CB) are promising targets for a number of diseases, including obesity, neuropathic pain, and multiple sclerosis, among others. Upon ligand-mediated activa...

In vitro determination of the CB1 efficacy of illicit synthetic cannabinoids.

The morbidity and mortality associated with recreational use of synthetic cannabinoid receptor agonists (SCRAs) may reflect strong activation of CB1 receptors and is a major health concern. The proper...

Identification and biochemical analyses of selective CB agonists.

Cannabinoid CB and CB receptors are activated by Δ-tetrahydrocannabinol, a psychoactive component of marijuana. The cannabinoid CB receptor is primarily located in the brain and is responsible for th...

5F-MDMB-PICA Metabolite Identification and Cannabinoid Receptor Activity.

According to EMCDDA, there were 179 different synthetic cannabinoids reported as of 2017. In the US, 5F-MDMB-PINACA, or 5F-ADB, accounted for 28% of cannabinoid seizures 2016-2018. The synthetic canna...

Strategies to develop selective CB receptor agonists from indole carboxamide synthetic cannabinoids.

Activation of the CB receptor is an attractive therapeutic strategy for the treatment of a wide range of inflammatory diseases. However, receptor subtype selectivity is necessary in order to circumven...

Clinical Trials [4560 Associated Clinical Trials listed on BioPortfolio]

Acute and Chronic Toxicity of Some Synthetic Cannabinoids in Assiut Psychiatric Hospitals

Synthetic cannabinoids (SCs) are new human-made mind-altering chemicals which are similar to chemicals found in the marijuana plant; they are recent to be used recreationally, especially b...

CB1R in Synthetic Psychoactive Cannabinoids

The purpose of this research study is to determine whether the CB1R availability is lower in synthetic psychoactive cannabinoid subjects using the most widely available synthetic psychoact...

Prediction and Testing of Antigenic Sites of the AIDS Virus, HTLV-III Recognized by T Lymphocytes for the Development of Synthetic Vaccines

Subjects are healthy adult volunteers either at high risk for HIV infection or already known to be seropositive, who will donate blood for in vitro tests of T-cell function and in vitro re...

The Effect of the GLP-1 Receptor Agonists on Blood Levels of Lipoprotein (a)

Lipoprotein (a) [Lp (a)] is an independent cardiovascular risk (CVR) both in the general population and in patients with type 2 diabetes mellitus (DM-2). Until now no effective treatment i...

Study of the Effects of Farnesoid X Receptor (FXR) Ligands on the Reactivation of Latent Provirus

The Farnesoid X receptor (FXR) is a nuclear receptor that controls the transcription of many genes involved in lipid and glucose metabolism. A recent study opens the hypothesis that Farnes...

Medical and Biotech [MESH] Definitions

Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.

A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.

A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.

Compounds that interact with and modulate the activity of CANNABINOID RECEPTORS.

Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.

Quick Search


DeepDyve research library

Relevant Topic

Public Health
Alternative Medicine Cleft Palate Complementary & Alternative Medicine Congenital Diseases Dentistry Ear Nose & Throat Food Safety Geriatrics Healthcare Hearing Medical Devices MRSA Muscular Dyst...


Searches Linking to this Article