A-836339

A-836339 is a drug developed by Abbott Laboratories that acts as a potent cannabinoid receptor full agonist. It is selective for CB2, with Ki values of 0.64 nM at CB2 vs 270 nM at the psychoactive CB1 receptor, but while it exhibits selective analgesic, anti-inflammatory and anti-hyperalgesic effects at low doses, its high efficacy at both targets results in typical cannabis-like effects appearing at higher doses, despite its low binding affinity for CB1.

Product information

CAS Number: 959746-77-1

Molecular Weight: 310.45

Formula: C16H26N2O2S

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

Smiles: COCCN1/C(=N/C(=O)C2C(C)(C)C2(C)C)/SC(C)=C1C

InChiKey: JKGIMVBQKSRTGX-VKAVYKQESA-N

InChi: 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/b17-14-

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 12 mg/mL (38.65 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

A-836339 was characterized extensively in various animal pain models. In the complete Freund's adjuvant model of inflammatory pain, A-836339 exhibits a potent CB(2) receptor-mediated antihyperalgesic effect that is independent of CB(1) or mu-opioid receptors. A-836339 has also demonstrated efficacies in the chronic constrain injury (CCI) model of neuropathic pain, skin incision, and capsaicin-induced secondary mechanical hyperalgesia models. Furthermore, no tolerance was developed in the CCI model after subchronic treatment with A-836339 for 5 days.

In Vivo:

The plantar aspect of the rat left hind paw was exposed through a hole in a sterile plastic drape, and a 1-cm longitudinal incision was made through the skin and fascia, starting 0.5 cm from the proximal edge of the heel and extending toward the toes. The plantaris muscle was elevated and incised longitudinally, leaving the muscle origin and insertion points intact. After homeostasis by application of gentle pressure, the skin was apposed with two mattress sutures using 5-0 nylon. Animals were then allowed to recover for 2 or 24 h after surgery, at which time mechanical allodynia was assessed.To test drug effects, rats were first acclimated for 20 min in inverted individual plastic containers (20*12.5*20 cm) on top of a suspended wire mesh grid, and A-836339 was injected intraperitoneally 30 min before testing for mechanical allodynia using calibrated von Frey filaments . von Frey filaments were presented perpendicularly to the plantar surface of the selected hind paw and then held in this position for approximately 8 s, with enough force to cause a slight bend of the filament. Positive responses included an abrupt withdrawal of the hind paw from the stimulus or flinching behavior immediately after removal of the stimulus. A 50% withdrawal threshold was determined using an up-down procedure.

References:

1. Mcgaraughty S , Chu K M , Yao B , et al. A CB 2, receptor agonist, A-836339, modulates wide dynamic range neuronal activity in neuropathic rats: Contributions of spinal and peripheral CB 2, receptors[J]. Neuroscience, 2009, 158(4):1652-1661.

Products are for research use only. Not for human use.