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MDA19: pharmacological profile of cannabinoid ligand

The cannabinoid receptor 2 (CB(2)) agonists are potential therapeutic targets in the treatment of neuropathic pain. The pharmacological profile of N'-[(3Z)-1-(1-hexyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]benzohydrazide (MDA19), a CB(2) agonist suggest MDA19 could be a analgesic for the treatment of neuropathic pain.

MDA19: pharmacological profile

MDA19 is a novel synthesized ligand of the CB1 and 2 receptors. ^[1]
MDA19 in reversed neuropathic pain in various neuropathic pain models in rats and in CB(2)(+/+) and CB(2)(-/-) mice.
MDA19 displayed 4-fold-higher affinity at the human CB(2) than at the human CB(1) receptor
MDA19 displayed a nearly 70-fold-higher affinity at the rat CB(2) than at the rat CB(1) receptor
In guanosine triphosphate (GTP)gamma[(35)S] functional assays, MDA19 behaved as an agonist at the human CB(1) and CB(2) receptors
In 3',5'-cyclic adenosine monophosphate (cAMP) assays, MDA19 behaved as an agonist at the rat CB(1) receptor and exhibited no functional activity at the rat CB(2) receptor.
In extracellular signal-regulated kinases 1 and 2 activation assays, MDA19 behaved as an agonist at the rat CB(2) receptor.
MDA19 attenuated tactile allodynia produced by spinal nerve ligation or paclitaxel in a dose-related manner in rats and CB(2)(+/+) mice but not in CB(2)(-/-) mice, indicating that CB(2) receptors mediated the effects of MDA19.

Conclusion:

MDA19 exhibits a distinctive in vitro functional profile at rat CB(2) receptors and behaved as a CB(1)/CB(2) agonist in vivo, characteristics of a protean agonist. ^[2]

June, Jan M. Keppel Hesselink, MD

Referenties

[1]: Diaz P, Xu J, Astruc-Diaz F, Pan HM, Brown DL, Naguib M. | Design and synthesis of a novel series of N-alkyl isatin acylhydrazone derivatives that act as selective cannabinoid receptor 2 agonists for the treatment of neuropathic pain. | J Med Chem. | 2008 Aug 28;51(16):4932-47. Epub 2008 Jul 31.

[2]: Xu JJ, Diaz P, Astruc-Diaz F, Craig S, Munoz E, Naguib M. | Pharmacological characterization of a novel cannabinoid ligand, MDA19, for treatment of neuropathic pain. | Anesth Analg. | 2010 Jul;111(1):99-109. Epub 2010 Jun 3.