TY  - JOUR
PY  - 2023//
TI  - Pharmacological insights emerging from the characterization of a large collection of synthetic cannabinoid receptor agonists designer drugs
JO  - Biomedicine and pharmacotherapy
A1  - Gioé-Gallo, Claudia
A1  - Ortigueira, Sandra
A1  - Brea, José
A1  - Raïch, Iu
A1  - Azuaje, Jhonny
A1  - Paleo, M. Rita
A1  - Majellaro, Maria
A1  - Loza, María Isabel
A1  - Salas, Cristian O.
A1  - García-Mera, Xerardo
A1  - Navarro, Gemma
A1  - Sotelo, Eddy
SP  - e114934
EP  - e114934
VL  - 164
IS  - 
N2  - Synthetic cannabinoid receptor agonists (SCRAs) constitute the largest and most defiant group of abuse designer drugs. These new psychoactive substances (NPS), developed as unregulated alternatives to cannabis, have potent cannabimimetic effects and their use is usually associated with episodes of psychosis, seizures, dependence, organ toxicity and death. Due to their ever-changing structure, very limited or nil structural, pharmacological, and toxicological information is available to the scientific community and the law enforcement offices. Here we report the synthesis and pharmacological evaluation (binding and functional) of the largest and most diverse collection of enantiopure SCRAs published to date. Our results revealed novel SCRAs that could be (or may currently be) used as illegal psychoactive substances. We also report, for the first time, the cannabimimetic data of 32 novel SCRAs containing an (R) configuration at the stereogenic center. The systematic pharmacological profiling of the library enabled the identification of emerging Structure-Activity Relationship (SAR) and Structure-Selectivity Relationship (SSR) trends, the detection of ligands exhibiting incipient cannabinoid receptor type 2 (CB(2)R) subtype selectivity and highlights the significant neurotoxicity of representative SCRAs on mouse primary neuronal cells. Several of the new emerging SCRAs are currently expected to have a rather limited potential for harm, as the evaluation of their pharmacological profiles revealed lower potencies and/or efficacies. Conceived as a resource to foster collaborative investigation of the physiological effects of SCRAs, the library obtained can contribute to addressing the challenge posed by recreational designer drugs.<p />  <p>Language: en</p>
LA  - en
SN  - 0753-3322
UR  - http://dx.doi.org/10.1016/j.biopha.2023.114934
ID  - ref1
ER  -