Arachidonylcyclopropylamide

JWH-073, a synthetic cannabinoid, is an analgesic chemical from the naphthoylindole family that acts as a full agonist at both the CB₁ and CB₂ cannabinoid receptors. It is somewhat selective for the CB₁ subtype, with affinity at this subtype approximately 5× the affinity at CB₂. The abbreviation JWH stands for John W. Huffman, one of the inventors of the compound.

AM-411 is an analgesic drug that is a cannabinoid agonist. It is a derivative of Δ8-THC substituted with an adamantyl group at the 3-position, demonstrating that the binding pocket for the alkyl chain at this position can accommodate significant bulk.

AM-906 (part of the AM cannabinoid series) is an analgesic drug which is a cannabinoid agonist. It is conformationally restricted by virtue of the double bond on its side chain, leading an increased affinity for and selectivity between CB₁ and CB₂ receptors. It is a potent and selective agonist for the CB₁ cannabinoid receptor, with a K_i of 0.8 nM at CB₁ and 9.5 nM at CB₂, a selectivity of almost 12x.

AM-905 (part of the AM cannabinoid series) is an analgesic drug which is a cannabinoid agonist. It is conformationally restricted by virtue of the double bond on its side chain, leading an increased affinity for and selectivity between CB₁ and CB₂ receptors. It is a potent and reasonably selective agonist for the CB₁ cannabinoid receptor, with a K_i of 1.2 nM at CB₁ and 5.3 nM at CB₂.

JWH-359 is a dibenzopyran "classical" cannabinoid drug, which is a potent and selective CB₂ receptor agonist, with a K_i of 13.0 nM and selectivity of around 220 times for CB₂ over CB₁ receptors. It is related to other dibenzopyran CB₂ agonists such as JWH-133 and L-759,656 but with a chiral side chain which has made it useful for mapping the shape of the CB₂ binding site. It was discovered by, and named after, John W. Huffman.

AM-694 (1-(5-fluoropentyl)-3-(2-iodobenzoyl)indole) is a designer drug that acts as a potent and selective agonist for the cannabinoid receptor CB₁. It is used in scientific research for mapping the distribution of CB₁ receptors.

A-836,339 is a drug developed by Abbott Laboratories that acts as a potent cannabinoid receptor full agonist. It is selective for CB₂, with K_i values of 0.64 nM at CB₂ vs 270 nM at the psychoactive CB₁ receptor, but while it exhibits selective analgesic, anti-inflammatory and anti-hyperalgesic effects at low doses, its high efficacy at both targets results in typical cannabis-like effects appearing at higher doses, despite its low binding affinity for CB₁. In 2012 A-836,339 was detected via X-ray crystallography in a "dubious product" sold in Japan, though the product was described as a white powder, not herbal incense, it was suggested to be for human consumption.

A-834,735 is a drug developed by Abbott Laboratories that acts as a potent cannabinoid receptor full agonist at both the CB₁ and CB₂ receptors, with a K_i of 12 nM at CB₁ and 0.21 nM at CB₂. Replacing the aromatic 3-benzoyl or 3-naphthoyl group found in most indole derived cannabinoids with the 3-tetramethylcyclopropylmethanone group of A-834,735 and related compounds imparts significant selectivity for CB₂, with most compounds from this group found to be highly selective CB₂ agonists with little affinity for CB₁. However, low nanomolar CB₁ binding affinity is retained with certain heterocyclic 1-position substituents such as (N-methylpiperidin-2-yl)methyl (cf. AM-1220, AM-1248), or the (tetrahydropyran-4-yl)methyl substituent of A-834,735, resulting in compounds that still show significant affinity and efficacy at both receptors despite being CB₂ selective overall.

A-796,260 is a drug developed by Abbott Laboratories that acts as a potent and selective cannabinoid CB₂ receptor agonist. Replacing the aromatic 3-benzoyl or 3-naphthoyl group found in most indole derived cannabinoids with the 3-tetramethylcyclopropylmethanone group, imparts significant selectivity for CB₂, and A-796,260 was found to be a highly selective CB₂ agonist with little affinity for CB₁, having a CB₂K_i of 4.6 nM vs 945 nM at CB₁. It has potent analgesic and anti-inflammatory actions in animal models, being especially effective in models of neuropathic pain, but without producing cannabis-like behavioral effects.

AM-1221 is a drug that acts as a potent and selective agonist for the cannabinoid receptor CB₂, with a K_i of 0.28 nM at CB₂ and 52.3 nM at the CB₁ receptor, giving it around 180 times selectivity for CB₂. The 2-methyl and 6-nitro groups on the indole ring both tend to increase CB₂ affinity while generally reducing affinity at CB₁, explaining the high CB₂ selectivity of AM-1221. However, despite this relatively high selectivity for CB₂, its CB₁ affinity is still too strong to make it useful as a truly selective CB₂ agonist, so the related compound AM-1241 is generally preferred for research purposes.

AM-630 (6-Iodopravadoline) is a drug that acts as a potent and selective inverse agonist for the cannabinoid receptor CB₂, with a K_i of 32.1 nM at CB₂ and 165x selectivity over CB₁, at which it acted as a weak partial agonist. It is used in the study of CB₂ mediated responses and has been used to investigate the possible role of CB₂ receptors in the brain. AM-630 is significant as one of the first indole derived cannabinoid ligands substituted on the 6-position of the indole ring, a position that has subsequently been found to be important in determining affinity and efficacy at both the CB₁ and CB₂ receptors, and has led to the development of many related derivatives.

AM-679 (part of the AM cannabinoid series) is a drug that acts as a moderately potent agonist for the cannabinoid receptors, with a K_i of 13.5 nM at CB₁ and 49.5 nM at CB₂. AM-679 was one of the first 3-(2-iodobenzoyl)indole derivatives that was found to have significant cannabinoid receptor affinity, and while AM-679 itself has only modest affinity for these receptors, it was subsequently used as a base to develop several more specialised cannabinoid ligands that are now widely used in research, including the potent CB₁ agonists AM-694 and AM-2233, and the selective CB₂ agonist AM-1241. AM-679 was first identified as having been sold as a cannabinoid designer drug in Hungary in 2011, along with another novel compound 1-pentyl-3-(1-adamantoyl)indole.

SR144528 is a drug that acts as a potent and highly selective CB₂ receptor inverse agonist, with a K_i of 0.6 nM at CB₂ and 400 nM at the related CB₁ receptor. It is used in scientific research for investigating the function of the CB₂ receptor, as well as for studying the effects of CB₁ receptors in isolation, as few CB₁ agonists that do not also show significant activity as CB₂ agonists are available. It has also been found to be an inhibitor of sterol O-acyltransferase, an effect that appears to be independent from its action on CB₂ receptors.

AM-1235 (1-(5-fluoropentyl)-3-(naphthalen-1-oyl)-6-nitroindole) is a drug that acts as a potent and reasonably selective agonist for the cannabinoid receptor CB₁.

AM-1220 is a drug that acts as a potent and moderately selective agonist for the cannabinoid receptor CB₁, with around 19 times selectivity for CB₁ over the related CB₂ receptor. It was originally invented in the early 1990s by a team led by Thomas D'Ambra at Sterling Winthrop, but has subsequently been researched by many others, most notably the team led by Alexandros Makriyannis at the University of Connecticut. The (piperidin-2-yl)methyl side chain of AM-1220 contains a stereocenter, so there are two enantiomers with quite different potency, the (R)-enantiomer having a K_i of 0.27 nM at CB₁ while the (S)-enantiomer has a much weaker K_i of 217 nM.

Arachidonyl-2'-chloroethylamide (ACEA) is a synthetic agonist of the CB₁ (CB1R). ACEA is considered to be a selective cannabinoid agonist as it binds primarily to the CB1R and has low affinity to the CB₂ (CB2R) (K_i = 1.4 nM for CB1R; K_i = 3100 nM for CB2R).

MN-25 (UR-12) is a drug invented by Bristol-Myers Squibb, that acts as a reasonably selective agonist of peripheral cannabinoid receptors. It has moderate affinity for CB₂ receptors with a K_i of 11 nM, but 22x lower affinity for the psychoactive CB₁ receptors with a K_i of 245 nM. The indole 2-methyl derivative has the ratio of affinities reversed however, with a K_i of 8 nM at CB₁ and 29 nM at CB₂, which contrasts with the usual trend of 2-methyl derivatives having increased selectivity for CB₂ (cf. JWH-018 vs JWH-007, JWH-081 vs JWH-098).

MDA-19 (also known as BZO-HEXOXIZID) is a drug that acts as a potent and selective agonist for the cannabinoid receptor CB₂, with reasonable selectivity over the psychoactive CB₁ receptor, though with some variation between species. In animal studies it was effective for the treatment of neuropathic pain, but did not affect rat locomotor activity in that specific study. The pharmacology of MDA-19 in rat cannabinoid receptors have been demonstrated to function differently than human cannabinoid receptors with MDA-19 binding to human CB₁ receptors 6.9× higher than rat CB₁ receptors.

AM-2389 is a classical cannabinoid derivative which acts as a potent and reasonably selective agonist for the CB₁ receptor, with a K_i of 0.16 nM, and 26× selectivity over the related CB₂ receptor. It has high potency in animal tests of cannabinoid activity, and a medium duration of action. Replacing the 1',1'-dimethyl substitution of the dimethylheptyl side chain of classical cannabinoids with cyclopropyl or cyclopentyl results in higher potency than cyclobutyl, but only the cyclobutyl derivatives show selectivity for CB₁ over CB₂. High selectivity for CB₁ over CB₂ is difficult to achieve (cf. AM-906, AM-1235), as almost all commonly used CB₁ agonists have similar or greater affinity for CB₂ than CB₁, and the only truly highly selective CB₁ agonists known as of 2012 are eicosanoid derivatives such as O-1812.

FUBIMINA is a synthetic cannabinoid that is the benzimidazole analog of AM-2201 and has been used as an active ingredient in synthetic cannabis products. It was first identified in Japan in 2013, alongside MEPIRAPIM.