Cannabinoid CB₂ receptor (human CB₂ Ki = 0.4 nM; rat CB₂ Ki = 0.8 nM; selectivity over CB₁ receptor > 200-fold). [3]

A-836339 exhibits high binding affinity at the human and rat CB₂ receptors, with Ki values of 0.4 nM and 0.8 nM, respectively. It has high selectivity over the CB₁ receptor (> 200-fold). [3]

A-836339 produced dose-dependent anti-hyperalgesic effects in the CFA-induced chronic inflammatory pain model in rats. Following intraperitoneal administration (1, 3, 10 μmol/kg), it significantly reversed CFA-induced decreases in paw withdrawal latency, achieving 80% effect at the highest dose with an ED₅₀ of 1.8 μmol/kg (95% CI = 1.5 – 2.2). The anti-hyperalgesic effect was blocked by the selective CB₂ antagonist SR144528 (10 μmol/kg, i.p.), but not by the selective CB₁ antagonist rimonabant (10 μmol/kg, i.p.), and was not reversed by the opioid receptor antagonist naloxone (10 mg/kg, i.p.). [3]
In the SNL model of neuropathic pain, systemic A-836339 (i.p.) attenuated mechanical allodynia in a dose-related manner with an ED₉₀ of 14.5 μmol/kg (95% CI: 11 – 19) and produced 67% reversal at 30 μmol/kg. The effect was blocked by SR144528 (10 μmol/kg, i.p.). [3]
In the CCI model of neuropathic pain, A-836339 (i.p., 30 μmol/kg) produced 71% reversal of mechanical allodynia, which was also blocked by SR144528 (10 μmol/kg, i.p.). [3]
Local administration via intra-DRG (100 nmol/rat) significantly reversed CFA-induced thermal hyperalgesia (65% reversal) and SNL-induced mechanical allodynia (45% reversal). Intrathecal administration (100 nmol/rat) produced significant reversal of SNL-induced mechanical allodynia (33% reversal) but did not significantly affect CFA-induced thermal hyperalgesia. Ipsilateral intraplantar administration of A-836339 (up to 100 nmol/i.paw) did not produce significant local effects; modest effects observed at 300 nmol/i.paw were also seen with contralateral administration, suggesting systemic absorption. [3]

Systemic administration: A-836339 was dissolved in 5% DMSO/95% PEG-400 (v/v) and administered intraperitoneally (i.p.) at a volume of 2 mL/kg, 30 minutes before behavioral testing. For antagonist studies, SR144528 or rimonabant were administered i.p. 15 minutes before A-836339. Naloxone was administered i.p. 20 minutes before A-836339. [3]
Local administration (intra-DRG and intrathecal): A-836339 was dissolved in 10% DMSO/90% hydroxyl-β-cyclodextrin (30%, w/w) in water (v/v) and administered at an injection volume of 10 μL, 30 minutes before behavioral testing. For intra-DRG administration, the catheter tip was positioned 1–2 mm dorsal to the exposed L5 DRG; for intrathecal administration, the catheter tip was advanced 8.5 cm caudally to the lumbar enlargement (L4-L6). [3]
Intraplantar administration: A-836339 was dissolved in the same vehicle and administered into the intra-plantar surface of the hind paw at a volume of 50 μL, 30 minutes before testing. [3]
CFA inflammatory pain model: Chronic inflammatory pain was induced by intraplantar injection of 150 μL of 50% CFA emulsion in PBS. Thermal hyperalgesia was assessed 48 hours post-CFA using a Hargreaves-type apparatus, with a cutoff of 20.48 seconds. Paw withdrawal latency was measured 30 minutes after drug administration. [3]
SNL neuropathic pain model: L5 and L6 spinal nerves were ligated unilaterally. Mechanical allodynia was assessed 7–14 days post-surgery using von Frey filaments with the up-down method. Paw withdrawal threshold was measured 30 minutes after drug administration. [3]
CCI neuropathic pain model: The right sciatic nerve was loosely ligated with four chromic gut ties. Mechanical allodynia was assessed 2–3 weeks post-surgery using von Frey filaments. [3]

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Systemic administration: A-836339 was dissolved in 5% DMSO/95% PEG-400 (v/v) and administered intraperitoneally (i.p.) at a volume of 2 mL/kg, 30 minutes before behavioral testing. For antagonist studies, SR144528 or rimonabant were administered i.p. 15 minutes before A-836339. Naloxone was administered i.p. 20 minutes before A-836339. [3]
Local administration (intra-DRG and intrathecal): A-836339 was dissolved in 10% DMSO/90% hydroxyl-β-cyclodextrin (30%, w/w) in water (v/v) and administered at an injection volume of 10 μL, 30 minutes before behavioral testing. For intra-DRG administration, the catheter tip was positioned 1–2 mm dorsal to the exposed L5 DRG; for intrathecal administration, the catheter tip was advanced 8.5 cm caudally to the lumbar enlargement (L4-L6). [3]
Intraplantar administration: A-836339 was dissolved in the same vehicle and administered into the intra-plantar surface of the hind paw at a volume of 50 μL, 30 minutes before testing. [3]
CFA inflammatory pain model: Chronic inflammatory pain was induced by intraplantar injection of 150 μL of 50% CFA emulsion in PBS. Thermal hyperalgesia was assessed 48 hours post-CFA using a Hargreaves-type apparatus, with a cutoff of 20.48 seconds. Paw withdrawal latency was measured 30 minutes after drug administration. [3]
SNL neuropathic pain model: L5 and L6 spinal nerves were ligated unilaterally. Mechanical allodynia was assessed 7–14 days post-surgery using von Frey filaments with the up-down method. Paw withdrawal threshold was measured 30 minutes after drug administration. [3]
CCI neuropathic pain model: The right sciatic nerve was loosely ligated with four chromic gut ties. Mechanical allodynia was assessed 2–3 weeks post-surgery using von Frey filaments. [3]

[1]. Characterization of a cannabinoid CB2 receptor-selective agonist, A-836339 [2,2,3,3-tetramethyl-cyclopropanecarboxylic acid [3-(2-methoxy-ethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide] using in vitro pharmacological assays, in vivo pa.

[2]. A CB(2) receptor agonist, A-836339, modulates wide dynamic range neuronal activity in neuropathic rats: contributions of spinal and peripheral CB(2) receptors. Neuroscience. 2009 Feb 18;158(4):1652-61.

[3]. Central and peripheral sites of action for CB? receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats. Br J Pharmacol. 2011 Jan;162(2):428-40.

A-836339 is a potent and selective CB₂ receptor agonist that demonstrates broad-spectrum efficacy in preclinical models of inflammatory and neuropathic pain. Its analgesic effects are mediated through CB₂ receptor activation, as they are blocked by the selective CB₂ antagonist SR144528 but not by the CB₁ antagonist rimonabant. Unlike the CB₂ agonist AM1241, the antinociceptive effects of A-836339 do not involve the μ-opioid receptor pathway (naloxone-insensitive). The compound exhibits relatively few off-target interactions, making it a useful tool for characterizing CB₂ receptor pharmacology. Both the dorsal root ganglia (DRG) and the spinal cord are important sites of action for its analgesic effects. [3]

C16H26N2O2S

310.456

310.171

959746-77-1

17754357

Light yellow to yellow solid powder

1.1±0.1 g/cm3

388.4±44.0 °C at 760 mmHg

188.7±28.4 °C

0.0±0.9 mmHg at 25°C

1.561

3.88

0

3

4

21

506

0

JKGIMVBQKSRTGX-UHFFFAOYSA-N

InChI=1S/C16H26N2O2S/c1-10-11(2)21-14(18(10)8-9-20-7)17-13(19)12-15(3,4)16(12,5)6/h12H,8-9H2,1-7H3

N-[3-(2-methoxyethyl)-4,5-dimethyl-1,3-thiazol-2-ylidene]-2,2,3,3-tetramethylcyclopropane-1-carboxamide

A-836339 A836339 A 836339 A 836,339 A836,339A-836,339

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~12 mg/mL (~38.65 mM)

Solubility in Formulation 1: ≥ 0.71 mg/mL (2.29 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.1 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 0.71 mg/mL (2.29 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.1 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 0.71 mg/mL (2.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.1 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)