Molecular Pharmacology of Synthetic Cannabinoids: Delineating CB1 Receptor-Mediated Cell Signaling

Autor: Haley K. Andersen, Kenneth B. Walsh
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Models
Molecular
Cannabinoid receptor
Adolescent
medicine.medical_treatment
Review
cell signaling assays
Pharmacology
Catalysis
Inorganic Chemistry
Adenylyl cyclase
lcsh:Chemistry
03 medical and health sciences
chemistry.chemical_compound
Structure-Activity Relationship
Young Adult
0302 clinical medicine
Receptor
Cannabinoid
CB1
Synthetic cannabinoids
medicine
Cannabinoid receptor type 2
Animals
Humans
G protein-coupled inwardly-rectifying potassium channel
Physical and Theoretical Chemistry
Receptor
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Molecular Structure
Chemistry
Cannabinoids
Organic Chemistry
molecular pharmacology
General Medicine
Molecular Pharmacology
Computer Science Applications
030104 developmental biology
nervous system
lcsh:Biology (General)
lcsh:QD1-999
Cannabinoid
synthetic cannabinoids
CB1 receptors
030217 neurology & neurosurgery
medicine.drug
Signal Transduction
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 6115, p 6115 (2020)
International Journal of Molecular Sciences
ISSN: 1661-6596
1422-0067
Popis: Synthetic cannabinoids (SCs) are a class of new psychoactive substances (NPSs) that exhibit high affinity binding to the cannabinoid CB1 and CB2 receptors and display a pharmacological profile similar to the phytocannabinoid (-)-trans-Δ9-tetrahydrocannabinol (THC). SCs are marketed under brand names such as K2 and Spice and are popular drugs of abuse among male teenagers and young adults. Since their introduction in the early 2000s, SCs have grown in number and evolved in structural diversity to evade forensic detection and drug scheduling. In addition to their desirable euphoric and antinociceptive effects, SCs can cause severe toxicity including seizures, respiratory depression, cardiac arrhythmias, stroke and psychosis. Binding of SCs to the CB1 receptor, expressed in the central and peripheral nervous systems, stimulates pertussis toxin-sensitive G proteins (Gi/Go) resulting in the inhibition of adenylyl cyclase, a decreased opening of N-type Ca2+ channels and the activation of G protein-gated inward rectifier (GIRK) channels. This combination of signaling effects dampens neuronal activity in both CNS excitatory and inhibitory pathways by decreasing action potential formation and neurotransmitter release. Despite this knowledge, the relationship between the chemical structure of the SCs and their CB1 receptor-mediated molecular actions is not well understood. In addition, the potency and efficacy of newer SC structural groups has not been determined. To address these limitations, various cell-based assay technologies are being utilized to develop structure versus activity relationships (SAR) for the SCs and to explore the effects of these compounds on noncannabinoid receptor targets. This review focuses on describing and evaluating these assays and summarizes our current knowledge of SC molecular pharmacology.
Databáze: OpenAIRE
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