JWH-015: Difference between revisions

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'''JWH-015''' is a chemical from the [[naphthoylindole]] family, which acts as a subtype-selective [[cannabinoid]] agonist. Its affinity for [[Cannabinoid receptor 2 (macrophage)|CB<sub>2</sub> receptors]] is 13.8nM, while its affinity for [[Cannabinoid receptor 1|CB<sub>1</sub>]] is 383nM, meaning that it binds almost 28x more strongly to CB<sub>2</sub> than CB<sub>1</sub>.<ref>Aung MM, Griffin G, Huffman JW, Wu MJ, Keel C, Yang B, Showalter VM, Abood ME, Martin BR. Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB<sub>1</sub> and CB<sub>2</sub> receptor binding. ''Drug and Alcohol Dependence'' 2000; 60:133-140.</ref> However it still displays some weak CB<sub>1</sub> activity, and is not as selective as newer drugs such as [[JWH-133]].<ref>Marriott KS, Huffman JW. Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor. ''Current Topics in Medicinal Chemistry''. 2008;8(3):187-204. PMID 18289088</ref> It has been shown to possess [[immunomodulatory]] effects,<ref>Ghosh S, Preet A, Groopman JE, Ganju RK. Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes. ''Molecular Immunology''. 2006 Jul;43(14):2169-79. PMID 16503355</ref><ref>Montecucco F, Burger F, Mach F, Steffens S. CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways. ''American Journal of Physiology. Heart and Circulatory Physiology''. 2008 Mar;294(3):H1145-55. PMID 18178718</ref> and CB<sub>2</sub> agonists may be useful in the treatment of pain and inflammation.<ref>Ehrhart J, Obregon D, Mori T, Hou H, Sun N, Bai Y, Klein T, Fernandez F, Tan J, Shytle RD. Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation. ''Journal of Neuroinflammation''. 2005 Dec 12;2:29. PMID 16343349</ref><ref>Romero-Sandoval A, Eisenach JC. Spinal cannabinoid receptor type 2 activation reduces hypersensitivity and spinal cord glial activation after paw incision. ''Anesthesiology''. 2007 Apr;106(4):787-94. PMID 17413917</ref> It was discovered and named after Dr. [[John W. Huffman]].
'''JWH-015''' is a chemical from the [[naphthoylindole]] family, which acts as a subtype-selective [[cannabinoid]] agonist. Its affinity for [[Cannabinoid receptor 2 (macrophage)|CB<sub>2</sub> receptors]] is 13.8nM, while its affinity for [[Cannabinoid receptor 1|CB<sub>1</sub>]] is 383nM, meaning that it binds almost 28x more strongly to CB<sub>2</sub> than CB<sub>1</sub>.<ref>Aung MM, Griffin G, Huffman JW, Wu MJ, Keel C, Yang B, Showalter VM, Abood ME, Martin BR. Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB<sub>1</sub> and CB<sub>2</sub> receptor binding. ''Drug and Alcohol Dependence'' 2000; 60:133-140.</ref> However it still displays some weak CB<sub>1</sub> activity, and is not as selective as newer drugs such as [[JWH-133]].<ref>{{cite journal | pmid = 18289088 | author-separator =, | author-name-separator= }}</ref> It has been shown to possess [[immunomodulatory]] effects,<ref>{{cite journal | pmid = 16503355 | author-separator =, | author-name-separator= }}</ref><ref>{{cite journal | pmid = 18178718 | author-separator =, | author-name-separator= }}</ref> and CB<sub>2</sub> agonists may be useful in the treatment of pain and inflammation.<ref>{{cite journal | pmid = 16343349 | author-separator =, | author-name-separator= }}</ref><ref>{{cite journal | pmid = 17413917 | author-separator =, | author-name-separator= }}</ref> It was discovered and named after Dr. [[John W. Huffman]].


==Metabolism==
==Metabolism==
JWH-015 has been shown ''in vitro'' to be metabolised primarily by [[hydroxylation]] and N-[[dealkylation]], and also by [[epoxidation]] of the [[naphthalene]] ring,<ref>Zhang Q, Ma P, Cole RB, Wang G. Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS. ''Analytical and Bioanalytical Chemistry''. 2006 Nov;386(5):1345-55. PMID 16955257</ref> similar to the metabolic pathways seen for other [[aminoalkylindole]] [[cannabinoids]] such as [[WIN 55,212-2]].<ref>Zhang Q, Ma P, Iszard M, Cole RB, Wang W, Wang G. In vitro metabolism of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate, a cannabinoid receptor agonist. ''Drug Metabolism and Disposition''. 2002 Oct;30(10):1077-86. PMID 12228183</ref> [[Benzo(a)pyrene#Toxicity|Epoxidation of polycyclic aromatic hydrocarbons]] can produce [[carcinogenic]] metabolites, although there is no evidence to show that JWH-015 or other aminoalkylindole cannabinoids are actually carcinogenic ''in vivo''.
JWH-015 has been shown ''in vitro'' to be metabolised primarily by [[hydroxylation]] and N-[[dealkylation]], and also by [[epoxidation]] of the [[naphthalene]] ring,<ref>Zhang Q, Ma P, Cole RB, Wang G. Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS. ''Analytical and Bioanalytical Chemistry''. 2006 Nov;386(5):1345-55. PMID 16955257</ref> similar to the metabolic pathways seen for other [[aminoalkylindole]] [[cannabinoids]] such as [[WIN 55,212-2]].<ref>{{cite journal | pmid = 12228183 | author-separator =, | author-name-separator= }}</ref> [[Benzo(a)pyrene#Toxicity|Epoxidation of polycyclic aromatic hydrocarbons]] can produce [[carcinogenic]] metabolites, although there is no evidence to show that JWH-015 or other aminoalkylindole cannabinoids are actually carcinogenic ''in vivo''.


{{cannabinoid-stub}}
{{cannabinoid-stub}}

Revision as of 23:57, 6 December 2010

JWH-015
Legal status
Legal status
  • In general: legal
Identifiers
  • (2-Methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.161.912 Edit this at Wikidata
Chemical and physical data
FormulaC23H21NO
Molar mass327.43 g/mol g·mol−1

JWH-015 is a chemical from the naphthoylindole family, which acts as a subtype-selective cannabinoid agonist. Its affinity for CB2 receptors is 13.8nM, while its affinity for CB1 is 383nM, meaning that it binds almost 28x more strongly to CB2 than CB1.[1] However it still displays some weak CB1 activity, and is not as selective as newer drugs such as JWH-133.[2] It has been shown to possess immunomodulatory effects,[3][4] and CB2 agonists may be useful in the treatment of pain and inflammation.[5][6] It was discovered and named after Dr. John W. Huffman.

Metabolism

JWH-015 has been shown in vitro to be metabolised primarily by hydroxylation and N-dealkylation, and also by epoxidation of the naphthalene ring,[7] similar to the metabolic pathways seen for other aminoalkylindole cannabinoids such as WIN 55,212-2.[8] Epoxidation of polycyclic aromatic hydrocarbons can produce carcinogenic metabolites, although there is no evidence to show that JWH-015 or other aminoalkylindole cannabinoids are actually carcinogenic in vivo.

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References

  1. ^ Aung MM, Griffin G, Huffman JW, Wu MJ, Keel C, Yang B, Showalter VM, Abood ME, Martin BR. Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB1 and CB2 receptor binding. Drug and Alcohol Dependence 2000; 60:133-140.
  2. ^ . PMID 18289088. {{cite journal}}: Cite has empty unknown parameter: |author-name-separator= (help); Cite journal requires |journal= (help); Missing or empty |title= (help); Unknown parameter |author-separator= ignored (help)
  3. ^ . PMID 16503355. {{cite journal}}: Cite has empty unknown parameter: |author-name-separator= (help); Cite journal requires |journal= (help); Missing or empty |title= (help); Unknown parameter |author-separator= ignored (help)
  4. ^ . PMID 18178718. {{cite journal}}: Cite has empty unknown parameter: |author-name-separator= (help); Cite journal requires |journal= (help); Missing or empty |title= (help); Unknown parameter |author-separator= ignored (help)
  5. ^ . PMID 16343349. {{cite journal}}: Cite has empty unknown parameter: |author-name-separator= (help); Cite journal requires |journal= (help); Missing or empty |title= (help); Unknown parameter |author-separator= ignored (help)
  6. ^ . PMID 17413917. {{cite journal}}: Cite has empty unknown parameter: |author-name-separator= (help); Cite journal requires |journal= (help); Missing or empty |title= (help); Unknown parameter |author-separator= ignored (help)
  7. ^ Zhang Q, Ma P, Cole RB, Wang G. Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS. Analytical and Bioanalytical Chemistry. 2006 Nov;386(5):1345-55. PMID 16955257
  8. ^ . PMID 12228183. {{cite journal}}: Cite has empty unknown parameter: |author-name-separator= (help); Cite journal requires |journal= (help); Missing or empty |title= (help); Unknown parameter |author-separator= ignored (help)


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