CP 55,940 explained

CP 55,940 is a synthetic cannabinoid which mimics the effects of naturally occurring THC (one of the psychoactive compounds found in cannabis). CP 55,940 was created by Pfizer in 1974 but was never marketed. It is currently used as a research tool to study the endocannabinoid system.^[1]

Pharmacology

CP 55,940 is 45 times more potent than Δ⁹-THC, and fully antagonized by rimonabant (SR141716A).^[2] It is considered a full agonist at both CB₁ and CB₂ receptors and has K_i values of 0.58 nM and 0.68 nM respectively, but is an antagonist at GPR55, the putative "CB₃" receptor.^[3] CP 55,940 binding has been detected in the cytosol of rat brain cerebral cortex.^[4] It can upregulate 5-HT_2A receptors in mice.^[5]

In vitro studies

CP 55,940 induced cell death in NG 108-15 Mouse neuroblastoma x Rat glioma hybrid brain cancer (genetically engineered mouse x rat brain cancer) cells.^{[6] [7]}

In vivo studies

CP 55,940 showed protective effects on rat brain mitochondria upon paraquat exposure.^[8]

It also showed neuroprotective effects by reducing intracellular calcium release and reducing hippocampal cell death in cultured neurons subjected to high levels of NMDA.^[9]

See also

• CP 42,096
• CP 47,497
• CP 55,244
• Cycloheptyl CP 55,940

Notes and References

1. Glass M, Dragunow M, Faull RL . Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain . Neuroscience . 77 . 2 . 299–318 . March 1997 . 9472392 . 10.1016/s0306-4522(96)00428-9 . 40213209 .
2. Rinaldi-Carmona M, Pialot F, Congy C, Redon E, Barth F, Bachy A, Brelière JC, Soubrié P, Le Fur G . 6 . Characterization and distribution of binding sites for [3H]-SR 141716A, a selective brain (CB1) cannabinoid receptor antagonist, in rodent brain . Life Sciences . 58 . 15 . 1239–47 . 1996 . 8614277 . 10.1016/0024-3205(96)00085-9 .
3. Kapur A, Zhao P, Sharir H, Bai Y, Caron MG, Barak LS, Abood ME . Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands . The Journal of Biological Chemistry . 284 . 43 . 29817–27 . October 2009 . 19723626 . 2785612 . 10.1074/jbc.M109.050187 . free .
4. Qureshi J, Saady M, Cardounel A, Kalimi M . Identification and characterization of a novel synthetic cannabinoid CP 55,940 binder in rat brain cytosol . Molecular and Cellular Biochemistry . 181 . 1–2 . 21–27 . April 1998 . 9562238 . 10.1023/A:1006855504094 . 6200670 .
5. Franklin JM, Carrasco GA . Cannabinoid receptor agonists upregulate and enhance serotonin 2A (5-HT(2A)) receptor activity via ERK1/2 signaling . Synapse . 67 . 3 . 145–59 . March 2013 . 23151877 . 3552103 . 10.1002/syn.21626 .
6. Tomiyama K, Funada M . Cytotoxicity of synthetic cannabinoids found in "Spice" products: the role of cannabinoid receptors and the caspase cascade in the NG 108-15 cell line . Toxicology Letters . 207 . 1 . 12–7 . November 2011 . 21907772 . 10.1016/j.toxlet.2011.08.021 .
7. Web site: General Cell Collection: NG108-15 . Public Health England Culture Collections .
8. Velez-Pardo C, Jimenez-Del-Rio M, Lores-Arnaiz S, Bustamante J . Protective effects of the synthetic cannabinoids CP55,940 and JWH-015 on rat brain mitochondria upon paraquat exposure . Neurochemical Research . 35 . 9 . 1323–32 . September 2010 . 20514518 . 10.1007/s11064-010-0188-1 . free . 11336/67604 . 821457 .
9. Zhuang SY, Bridges D, Grigorenko E, McCloud S, Boon A, Hampson RE, Deadwyler SA . Cannabinoids produce neuroprotection by reducing intracellular calcium release from ryanodine-sensitive stores . Neuropharmacology . 48 . 8 . 1086–96 . June 2005 . 15910885 . 10.1016/j.neuropharm.2005.01.005 . 14953725 .