Abnormal cannabidiol

Abnormal cannabidiol
Identifiers
IUPAC name
  • 4-[(1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H30O2
Molar mass314.46 g·mol−1
3D model (JSmol)
SMILES
  • CCCCCC1=CC(=CC(=C1[C@H]2C=C(CC[C@H]2C(=C)C)C)O)O
InChI
  • InChI=1S/C21H30O2/c1-5-6-7-8-16-12-17(22)13-20(23)21(16)19-11-15(4)9-10-18(19)14(2)3/h11-13,18-19,22-23H,2,5-10H2,1,3-4H3/t18-,19-/m0/s1 checkY
  • Key:YWEZXUNAYVCODW-OALUTQOASA-N checkY
 ☒NcheckY (what is this?)  (verify)

Abnormal cannabidiol (Abn-CBD) is a synthetic regioisomer of cannabidiol, which unlike most other cannabinoids produces vasodilator effects, lowers blood pressure, and induces cell migration, cell proliferation and mitogen-activated protein kinase activation in microglia, but without producing any psychoactive effects.[1][2]

Receptor activity

It has been shown that the actions of abnormal cannabidiol are mediated through a site separate from the CB1 and CB2 receptors,[2][3] which responds to abnormal cannabidiol, O-1602, and the endogenous ligands: anandamide (AEA), N-arachidonoyl glycine (NAGly) and N-arachidonoyl L-serine.[2][4][5][6] Multiple lines of evidence support the proposed identification of this novel target in microglia as the previously "orphan" receptor GPR18.[2] Another possible target of abnormal cannabidiol is GPR55, which has also received much attention as a putative cannabinoid receptor,[7][8] although a growing body of evidence points to lysophosphatidylinositol (LPI) as the endogenous ligand for GPR55.[9][10] Further research suggests there are yet more additional cannabinoid receptors.[11][12][13][14]

Pharmacodynamics

Research of the effects on abnormal cannabidiol in mice has indicated that atypical cannabinoids have therapeutic potential in a variety of inflammatory conditions, including those of the gastrointestinal tract. After inducing colitis by means of trinitrobenzene sulfonic acid, wound healing of both human umbilical vein endothelial and epithelial cells was enhanced by the Abn-CBD.[15]

See also

References

  1. ↑ Adams, MD; Earnhardt, JT; Martin, BR; Harris, LS; Dewey, WL; Razdan, RK (1977). "A cannabinoid with cardiovascular activity but no overt behavioral effects". Experientia. 33 (9): 1204–1205. doi:10.1007/BF01922330. PMID 891878. S2CID 21488700.
  2. 1 2 3 4 McHugh D, Hu SS, Rimmerman N, Juknat A, Vogil Z, Walker JM, Bradshaw HB (March 2010). "N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor". BMC Neuroscience. 11: 44. doi:10.1186/1471-2202-11-44. PMC 2865488. PMID 20346144.
  3. ↑ Jarai, Z. (1999). "Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors". Proceedings of the National Academy of Sciences. 96 (24): 14136–14141. Bibcode:1999PNAS...9614136J. doi:10.1073/pnas.96.24.14136. PMC 24203. PMID 10570211.
  4. ↑ Walter, L; Franklin, A; Witting, A; Wade, C; Xie, Y; Kunos, G; MacKie, K; Stella, N (2003). "Nonpsychotropic cannabinoid receptors regulate microglial cell migration". Journal of Neuroscience. 23 (4): 1398–1405. doi:10.1523/JNEUROSCI.23-04-01398.2003. PMC 6742252. PMID 12598628.
  5. ↑ Offertáler, L; Mo, FM; Bátkai, S; Liu, J; Begg, M; Razdan, RK; Martin, BR; Bukoski, RD; Kunos, G (2003). "Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor". Molecular Pharmacology. 63 (3): 699–705. doi:10.1124/mol.63.3.699. PMID 12606780.
  6. ↑ Milman, G; Maor, Y; Abu-Lafi, S; Horowitz, M; Gallily, R; Batkai, S; Mo, FM; Offertaler, L; Pacher, P; Kunos, G; Mechoulam, R (2006). "N-arachidonoyl l-serine, an endocannabinoid-like brain constituent with vasodilatory properties". Proceedings of the National Academy of Sciences of the United States of America. 103 (7): 2428–2433. Bibcode:2006PNAS..103.2428M. doi:10.1073/pnas.0510676103. PMC 1413724. PMID 16467152.
  7. ↑ McCollum, L; Howlett, AC; Mukhopadhyay, S (2007). "Anandamide-mediated CB1/CB2 cannabinoid receptor—independent nitric oxide production in rabbit aortic endothelial cells". The Journal of Pharmacology and Experimental Therapeutics. 321 (3): 930–937. doi:10.1124/jpet.106.117549. PMID 17379772. S2CID 24492397.
  8. ↑ Ryberg, E; Larsson, N; Sjögren, S; Hjorth, S; Hermansson, NO; Leonova, J; Elebring, T; Nilsson, K; Drmota, T; Greasley, PJ (2007). "The orphan receptor GPR55 is a novel cannabinoid receptor". British Journal of Pharmacology. 152 (7): 1092–1101. doi:10.1038/sj.bjp.0707460. PMC 2095107. PMID 17876302.
  9. ↑ Kapur, A; Zhao, P; Sharir, H; Bai, Y; Caron, MG; Barak, LS; Abood, ME (2009). "Atypical Responsiveness of the Orphan Receptor GPR55 to Cannabinoid Ligands". The Journal of Biological Chemistry. 284 (43): 29817–29827. doi:10.1074/jbc.M109.050187. PMC 2785612. PMID 19723626.
  10. ↑ Henstridge, CM; Balenga, NA; Ford, LA; Ross, RA; Waldhoer, M; Irving, AJ (2009). "The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation". The FASEB Journal. 23 (1): 183–193. doi:10.1096/fj.08-108670. PMID 18757503. S2CID 27142069.
  11. ↑ Brown AJ (November 2007). "Novel cannabinoid receptors". British Journal of Pharmacology. 152 (5): 567–575. doi:10.1038/sj.bjp.0707481. PMC 2190013. PMID 17906678.
  12. ↑ Johns, D. G.; Behm, D. J.; Walker, D. J.; Ao, Z.; Shapland, E. M.; Daniels, D. A.; Riddick, M.; Dowell, S.; Staton, P. C.; Green, P.; Shabon, U.; Bao, W.; Aiyar, N.; Yue, T. -L.; Brown, A. J.; Morrison, A. D.; Douglas, S. A. (2009). "The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects". British Journal of Pharmacology. 152 (5): 825–831. doi:10.1038/sj.bjp.0707419. PMC 2190033. PMID 17704827.
  13. ↑ McHugh, D; Tanner, C; Mechoulam, R; Pertwee, RG; Ross, RA (2008). "Inhibition of human neutrophil chemotaxis by endogenous cannabinoids and phytocannabinoids: evidence for a site distinct from CB1 and CB2". Molecular Pharmacology. 73 (2): 441–450. doi:10.1124/mol.107.041863. PMID 17965195. S2CID 15182303.
  14. ↑ Kreutz, S; Koch, M; Böttger, C; Ghadban, C; Korf, HW; Dehghani, F (2009). "2-Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal-cannabidiol-sensitive receptors on microglial cells". Glia. 57 (3): 286–294. doi:10.1002/glia.20756. PMID 18837048. S2CID 37531270.
  15. ↑ Krohn, RM; Parsons, SA; Fichna, J; Patel, KD; Yates, RM; Sharkey, KA; Storr, MA (2016). "Abnormal cannabidiol attenuates experimental colitis in mice, promotes wound healing and inhibits neutrophil recruitment". Journal of Inflammation. 13 (21): 21. doi:10.1186/s12950-016-0129-0. PMC 4944257. PMID 27418880.
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