Cannabinoid receptor is a kind of cell membrane receptor in the G protein-coupled receptor superfamily. Specifically, the cannabinoid receptor contains seven transmembrane domains. Besides, three kinds of ligands can endogenous cannabinoid receptors by mammary gland; phytocannabinoid; and synthetic cannabinoid. The endocannabinoid system consists of endocannabinoids (endocannabinoids), cannabinoid receptors, and enzymes that synthesize and degrade endocannabinoids.
The CB1 receptor is in neurons and widely distributed in the whole central nervous system, including areas involved in the pain process. While the CB2 receptor is mainly expressed in immune cells. Moreover, the CB1 receptor in the central nervous system mediates the psychoactive and analgesic effects of cannabinoids. Recent studies have shown that both CB1 and CB2 receptors are in peripheral sensory nerve fibers, and peripheral CB1 and cb2rece can mediate analgesia. In addition, CB1 and CB2 mainly couples with inhibitory G protein and have the same pharmacological effects as other GPCRs. Today, we will introduce an orally active, high-affinity cannabinoid CB1/CB2 receptor agonist，AZD1940.
AZD1940 is an Orally Active Cannabinoid CB1/CB2 Receptor Agonist
First of all, AZD1940 is an orally active, high-affinity cannabinoid CB1/CB2 receptor agonist. Meanwhile, AZD1940 is a complete agonist with pKi values of 7.93 and 9.06 at human CB1R and CB2R, respectively. Nonetheless, AZD1940 shows a robust analgesic action. Particularly, AZD1940 binds with high affinity to human, rat, and mouse CB1 and CB2 receptors and displays full agonism at both receptors in all three species.
In the second place, AZD1940 produces robust analgesia in different models of inflammatory and neuropathic pain when given orally to rats. AZD1940 shows low brain uptake at analgesic doses in both rats and primates. Additionally, AZD1940 is a candidate drug for the treatment of neuropathic pain through pharmacological effects on CB1R and CB2R.
All in all, AZD1940 is an orally active, high-affinity cannabinoid CB1/CB2 receptor agonist.
Jarkko Kalliomäki, et al. Clin Exp Pharmacol Physiol. 2013 Mar;40(3):212-8.