AM-694

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AM-694
File:AM-694-2D-skeletal.svg
Systematic (IUPAC) name
1-[(5-fluoropentyl)-1H-indol-3-yl]-(2-iodophenyl)methanone
Legal status
Legal status
  • Legal
Identifiers
PubChem CID 9889172
Chemical data
Formula C20H19FINO
Molar mass 435.273 g/mol[[Script error: No such module "String".]]
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AM-694 (1-(5-fluoropentyl)-3-(2-iodobenzoyl)indole) is a drug which acts as a potent and selective agonist for the cannabinoid receptor CB1, with a Ki of 0.08nM at CB1 and 18x selectivity over the related CB2 receptor.[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 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, 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.[3][4] 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.

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. Millington JE, Pattison FLM. TOXIC FLUORINE COMPOUNDS: XII. ESTERS OF ω-FLUOROALCOHOLS. Canadian Journal of Chemistry. 1956 Nov;34(11):1532-1541.
  4. Pattison FLM, Howell WC, Woolford RG. TOXIC FLUORINE COMPOUNDS: XIII. ω-FLUOROALKYL ETHERS. Canadian Journal of Chemistry. 1957 Feb;35(2):141-148.