MDA7: a novel selective agonist for CB2 receptors that prevents allodynia in rat neuropathic pain models.
OBJECTIVE
There is growing interest in using cannabinoid type 2 (CB(2)) receptor agonists for the treatment of neuropathic pain. In this report, we describe the pharmacological characteristics of MDA7 (1-[(3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl)carbonyl]piperidine), a novel CB(2) receptor agonist.


METHODS
We characterized the pharmacological profile of MDA7 by using radioligand-binding assays and in vitro functional assays at human cannabinoid type 1 (CB(1)) and CB(2) receptors. In vitro functional assays were performed at rat CB(1) and CB(2) receptors. The effects of MDA7 in reversing neuropathic pain were assessed in spinal nerve ligation and paclitaxel-induced neuropathy models in rats.


RESULTS
MDA7 exhibited selectivity and agonist affinity at human and rat CB(2) receptors. MDA7 treatment attenuated tactile allodynia produced by spinal nerve ligation or by paclitaxel in a dose-related manner. These effects were selectively antagonized by a CB(2) receptor antagonist but not by CB(1) or opioid receptor antagonists. MDA7 did not affect rat locomotor activity.


CONCLUSIONS
MDA7, a novel selective CB(2) agonist, was effective in suppressing neuropathic nociception in two rat models without affecting locomotor behaviour. These results confirm the potential for CB(2) agonists in the treatment of neuropathic pain.
Naguib
M
M
1Department of Anesthesiology and Pain Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. naguib@mdanderson.org
Diaz
P
P
Xu
J J
JJ
Astruc-Diaz
F
F
Craig
S
S
Vivas-Mejia
P
P
Brown
D L
DL
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008026:Ligation; D009043:Motor Activity / Q000187:drug effects; D009437:Neuralgia / Q000188:drug therapy*; D017239:Paclitaxel; D010147:Pain Measurement; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D011869:Radioligand Assay; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D013045:Species Specificity; D013127:Spinal Nerves / Q000503:physiopathology
C534147:1-((3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl)carbonyl)piperidine; D000700:Analgesics; D001572:Benzofurans; D010880:Piperidines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D017239:Paclitaxel