cannabinoid cb2 receptor antagonists  (Solvay Pharmaceuticals)

Journal: ACS Omega

Article Title: Receptor-Selective Modulation of Cannabinoid Signaling by Cardamonin: Integrating Molecular Dynamics, Free Energy Calculations, and Behavioral Validation

doi: 10.1021/acsomega.5c10026

Figure Lengend Snippet: Schematic overview of the study design combining computational and behavioral approaches. Cardamonin, a chalcone derivative, was evaluated for its interaction with cannabinoid receptors CB1 and CB2 using molecular dynamics simulations and MM/PBSA analyses. Parallel in vivo behavioral assaysVon Frey and Hargreaves testswere conducted in mice to assess mechanical and thermal antinociception, respectively.

Article Snippet: Cardamonin (MedChemExpress LLC, USA) and selective cannabinoid receptor 1 (CB1) antagonists SR141716 (MedChemExpress LLC, USA) and selective cannabinoid receptor 2 (CB2) antagonist SR144528 (MedChemExpress LLC, USA) were dissolved in dimethyl sulfoxide [DMSO], Tween 20 and diluted with saline at a ratio of 5:5:90 for intraperitoneal (i.p.) administration.

Techniques: In Vivo

Journal: ACS Omega

Article Title: Receptor-Selective Modulation of Cannabinoid Signaling by Cardamonin: Integrating Molecular Dynamics, Free Energy Calculations, and Behavioral Validation

doi: 10.1021/acsomega.5c10026

Figure Lengend Snippet: Docking poses of cardamonin with CB1 (A) and CB2 (B) receptors. (A) Cardamonin binds to CB1 with −8.7 kcal/mol, forming hydrogen bonds (SER 505 , ILE 267 ), hydrophobic contacts (PHE 170 , VAL 196 , LEU 193 , PHE 200 ), and a π-cation interaction (HIS 178 ). (B) In CB2 (−8.0 kcal/mol), cardamonin engages in hydrophobic interactions and a π-stacking (PHE117). Interaction types: hydrogen bonds (blue), hydrophobic (gray dashed), π-cation (orange dashed), π-stacking (green dashed).

Article Snippet: Cardamonin (MedChemExpress LLC, USA) and selective cannabinoid receptor 1 (CB1) antagonists SR141716 (MedChemExpress LLC, USA) and selective cannabinoid receptor 2 (CB2) antagonist SR144528 (MedChemExpress LLC, USA) were dissolved in dimethyl sulfoxide [DMSO], Tween 20 and diluted with saline at a ratio of 5:5:90 for intraperitoneal (i.p.) administration.

Techniques:

Journal: ACS Omega

Article Title: Receptor-Selective Modulation of Cannabinoid Signaling by Cardamonin: Integrating Molecular Dynamics, Free Energy Calculations, and Behavioral Validation

doi: 10.1021/acsomega.5c10026

Figure Lengend Snippet: Hydrogen bond interaction snapshots between cardamonin and cannabinoid receptors CB1 (A) and CB2 (B) at selected time points from molecular dynamics simulations. Each frame corresponds to a representative structure at 100, 250, 500, and 750 ns. Hydrogen bonds are depicted as red dashed lines with annotated distances (Å). In CB1, dynamic repositioning of the ligand allows alternating interactions with residues such as HSD 178 , ILE 267 , PHE 189 , ASP 184 , SER 173 , and LEU 193 . In contrast, the CB2 complex demonstrates a more consistent hydrogen bonding profile, particularly with SER 285 and GLY 284 . These interactions reflect the temporal stability and flexibility of ligand–receptor engagement during the simulation trajectory.

Article Snippet: Cardamonin (MedChemExpress LLC, USA) and selective cannabinoid receptor 1 (CB1) antagonists SR141716 (MedChemExpress LLC, USA) and selective cannabinoid receptor 2 (CB2) antagonist SR144528 (MedChemExpress LLC, USA) were dissolved in dimethyl sulfoxide [DMSO], Tween 20 and diluted with saline at a ratio of 5:5:90 for intraperitoneal (i.p.) administration.

Techniques:

Journal: ACS Omega

Article Title: Receptor-Selective Modulation of Cannabinoid Signaling by Cardamonin: Integrating Molecular Dynamics, Free Energy Calculations, and Behavioral Validation

doi: 10.1021/acsomega.5c10026

Figure Lengend Snippet: Principal Component Analysis (PCA) of CB1 and CB2 receptor complexes. (A) PCA projection of CB1 control (black) and cardamonin-bound complex (red) onto the first two principal components. Cardamonin binding induces broader conformational sampling. (B) PCA projection of CB2 control (black) and cardamonin-bound complex (red), showing overlapping conformational space and reduced ligand impact.

Article Snippet: Cardamonin (MedChemExpress LLC, USA) and selective cannabinoid receptor 1 (CB1) antagonists SR141716 (MedChemExpress LLC, USA) and selective cannabinoid receptor 2 (CB2) antagonist SR144528 (MedChemExpress LLC, USA) were dissolved in dimethyl sulfoxide [DMSO], Tween 20 and diluted with saline at a ratio of 5:5:90 for intraperitoneal (i.p.) administration.

Techniques: Control, Binding Assay, Sampling

Journal: ACS Omega

Article Title: Receptor-Selective Modulation of Cannabinoid Signaling by Cardamonin: Integrating Molecular Dynamics, Free Energy Calculations, and Behavioral Validation

doi: 10.1021/acsomega.5c10026

Figure Lengend Snippet: (A) Mechanical paw withdrawal threshold (mean ± SEM) in the Von Frey test. SHM and CDM groups displayed high thresholds (normal sensitivity), while VHC, CB1 – , and CB2 – groups exhibited mechanical allodynia. Co-treatment with cardamonin (CDM+CB1 – and CDM+CB2 – ) partially restored pain thresholds. (B) Thermal paw withdrawal latency (mean ± SEM) in the Hargreaves test. SHM group showed normal latency. CB1 – , CB2 – , and VHC groups exhibited thermal hyperalgesia. Cardamonin (CDM) increased latency significantly, and cotreatment with CB1 – or CB2 – partially restored thermal sensitivity.

Article Snippet: Cardamonin (MedChemExpress LLC, USA) and selective cannabinoid receptor 1 (CB1) antagonists SR141716 (MedChemExpress LLC, USA) and selective cannabinoid receptor 2 (CB2) antagonist SR144528 (MedChemExpress LLC, USA) were dissolved in dimethyl sulfoxide [DMSO], Tween 20 and diluted with saline at a ratio of 5:5:90 for intraperitoneal (i.p.) administration.

Techniques:

Journal: Brazilian Journal of Medical and Biological Research

Article Title: Kahweol, a natural diterpene from coffee, induces peripheral antinociception by endocannabinoid system activation

doi: 10.1590/1414-431x2021e11071

Figure Lengend Snippet: Figure 1. Schematic diagram of the experimental protocol. A, Kahweol (Kah) was administered 175 min after the local administration of prostaglandin E2 (PGE2) (2 mg) and the antinociceptive response was measured prior to and 180 min, 195 min, and 210 min after PGE2 injection. B, Kah was administered in the right hind paw 175 min after local injection of PGE2. The cannabinoid drugs AM251, AM630, MAFP, JZL184, or VDM11 were given 10 min prior (165 min) to Kah intraplantar administration and measurements were performed prior to and 180 min after PGE2 administration.

Article Snippet: The CB1 cannabinoid receptor antagonist AM251 (N-[piperidin-1-yl]-5-[4-iodophenyl]-1-[2,4-dichlorophenyl]-4methyl-1H-pyrazole-3-carboxamide; purity499%; Tocris) (20, 40, 80 mg/paw) and the CB2 cannabinoid receptor antagonist AM630 (6-Iodo-2-methyl-1-[2-{4-morpholinyl}ethyl]1H-indol-3-yl [4-ethoxyphenyl] methanone; purity 498%; Tocris) (100 mg/paw) were dissolved in 10% DMSO, whereas the hyperalgesic agent PGE2 (purity X93%; Sigma-Aldrich, USA) was dissolved in 2% ethanol.

Techniques: Injection

Journal: Brazilian Journal of Medical and Biological Research

Article Title: Kahweol, a natural diterpene from coffee, induces peripheral antinociception by endocannabinoid system activation

doi: 10.1590/1414-431x2021e11071

Figure Lengend Snippet: Figure 4. The CB2 receptor antagonist did not block kahweol- induced peripheral antinociception in hyperalgesic paws. The antinociceptive response was measured by the paw pressure test. Prostaglandin E2 (PGE2) injection (2 mg/paw) was done at time 0, AM630 (100 mg/paw) was injected at time 165 min, and kahweol (Kah; 80 mg/paw) was given at 175 min. Measurements were made prior to and 180 min after PGE2 administration. Data are reported as means±SE (n=5) of D nociceptive threshold measured in grams (g). *Po0.05 compared to PGE2 + Veh 2 + Veh 3-injected group (ANOVA and Bonferroni’s test). There was no significant difference between (PGE2 + Veh 2 + Kah 80) and (PGE2 + AM630 100 + Kah 80)-injected groups. Veh (vehicle) 2: 10% DMSO in saline; Veh 3: sterile saline solution (0.9% NaCl).

Article Snippet: The CB1 cannabinoid receptor antagonist AM251 (N-[piperidin-1-yl]-5-[4-iodophenyl]-1-[2,4-dichlorophenyl]-4methyl-1H-pyrazole-3-carboxamide; purity499%; Tocris) (20, 40, 80 mg/paw) and the CB2 cannabinoid receptor antagonist AM630 (6-Iodo-2-methyl-1-[2-{4-morpholinyl}ethyl]1H-indol-3-yl [4-ethoxyphenyl] methanone; purity 498%; Tocris) (100 mg/paw) were dissolved in 10% DMSO, whereas the hyperalgesic agent PGE2 (purity X93%; Sigma-Aldrich, USA) was dissolved in 2% ethanol.

Techniques: Blocking Assay, Randall–Selitto Test, Injection, Saline, Sterility