AM-694
Encyclopedia
AM-694 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.
(being 1.44nm at CB2) 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.. 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. 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.
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
for the cannabinoid receptor
Cannabinoid receptor
The cannabinoid receptors are a class of cell membrane receptors under the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains...
CB1, with a Ki
Dissociation constant
In chemistry, biochemistry, and pharmacology, a dissociation constant is a specific type of equilibrium constant that measures the propensity of a larger object to separate reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt splits up into...
of 0.08nM at CB1 and 18x selectivity over the related CB2
Cannabinoid receptor 2 (macrophage)
Cannabinoid receptor 2 , also known as CB2 or CNR2, is a G protein-coupled receptor from the cannabinoid receptor family, which in humans is encoded by the CNR2 gene...
receptor.
(being 1.44nm at CB2) It is unclear what is responsible for this unusually high CB1 binding affinity, but it makes the 18F
Fluorine-18
Fluorine-18 is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380 u and its half-life is 109.771 minutes....
radiolabelled
Isotopic labeling
Isotopic labeling is a technique for tracking the passage of a sample of substance through a system. The substance is 'labeled' by including unusual isotopes in its chemical composition...
derivative of AM-694 useful for mapping the distribution of CB1 receptors in the body.. No public data about AM-694 metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
is known.
AM-694 has already emerged as a designer drug
Designer drug
Designer drug is a term used to describe drugs that are created to get around existing drug laws, usually by preparing analogs or derivatives of existing drugs by modifying their chemical structure to varying degrees, or less commonly by finding drugs with entirely different chemical structures...
. 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. Fluoroacetate is also produced in similar fashion by S-dealkylation of 2C-T-21
2C-T-21
2C-T-21 is a psychedelic phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. It was the first psychedelic drug known to contain six different chemical elements in the structure.-Chemistry:...
, 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.