AM-694

AM-694

Systematic (IUPAC) name
1-[(5-fluoropentyl)-1H-indol-3-yl]-(2-iodophenyl)methanone
Clinical data
Pregnancy cat.	?
Legal status	Legal
Identifiers
CAS number	335161-03-0 Y
ATC code	?
PubChem	CID 9889172
ChemSpider	8064843 Y
Chemical data
Formula	C20H19FINO
Mol. mass	435.273 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C20H19FINO/c21-12-6-1-7-13-23-14-17(15-8-3-5-11-19(15)23)20(24)16-9-2-4-10-18(16)22/h2-5,8-11,14H,1,6-7,12-13H2 Y Key:LFFIIZFINPPEMC-UHFFFAOYSA-N Y
Y(what is this?)  (verify)

This article includes a list of references, but its sources remain unclear because it has insufficient inline citations. Please help to improve this article by introducing more precise citations. (May 2011)

AM-694 (1-(5-fluoropentyl)-3-(2-iodobenzoyl)indole) is a drug that acts as a potent and selective agonist for the cannabinoid receptor CB₁, with a K_i of 0.08nM at CB₁ and 18x selectivity over the related CB₂ receptor. (being 1.44nm at CB2)^[1] It is unclear what is responsible for this unusually high CB₁ binding affinity, but it makes the ¹⁸F radiolabelled derivative of AM-694 useful for mapping the distribution of CB₁ receptors in the body.^[2]. No public data about AM-694 metabolism is known.

AM-694 has already emerged as a designer drug. Concerns have been raised^{[by whom?]} over the possible toxicity of this compound, due to its likely metabolism to ω-fluoroalkanoic acids. Studies of the metabolism of related compounds show that the first step is the N-dealkylation of the indole nitrogen^[3], which in this case yields 5-fluoropentanoic acid, which is then further metabolised to 3-fluoropropanoic acid. Terminal monofluoroalkanes with even numbers of carbons are ultimately metabolized into fluoroacetate, which is a potent toxin primarily used as a rodenticide and has the potential to bioaccumulate. As AM-694 contains a five carbon chain, fluoroacetate is unlikely to be produced as a metabolite, with the substantially less toxic 3-fluoropropanoic acid being produced instead. The 4-fluorobutyl and 6-fluorohexyl homologues of AM-694 will however produce fluoroacetate as a metabolite and so may be significantly more toxic.^[4][5] Fluoroacetate is also produced in similar fashion by S-dealkylation of 2C-T-21, another designer drug, so death from acute fluoroacetate poisoning appears unlikely following consumption of these drugs, with concerns instead relating to the potential for chronic toxicity with extended use.

See also

• AM-679
• AM-2201
• AM-2233

References

1. ^ WO patent 200128557, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2001-06-07  
2. ^ Willis PG, Katoch-Rouse R, Horti AG. Regioselective F-18 radiolabeling of AM694, a CB1 cannabinoid receptor ligand. Journal of Labelled Compounds and Radiopharmaceuticals 2003;46(9):799-804. doi: 10.1002/jlcr.720
3. ^ 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
4. ^ Millington JE, Pattison FLM. TOXIC FLUORINE COMPOUNDS: XII. ESTERS OF ω-FLUOROALCOHOLS. Canadian Journal of Chemistry. 1956 Nov;34(11):1532-1541.
5. ^ Pattison FLM, Howell WC, Woolford RG. TOXIC FLUORINE COMPOUNDS: XIII. ω-FLUOROALKYL ETHERS. Canadian Journal of Chemistry. 1957 Feb;35(2):141-148.

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