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.
AMG-36 (part of the AM cannabinoid series) is an analgesic drug which is a cannabinoid agonist. It is a derivative of Δ8-THC substituted with a cyclopentane group on the 3-position side chain. AMG-36 is a potent agonist at both CB1 and CB2 with moderate selectivity for CB1, with a Ki of 0.45 nM at CB1 vs 1.92 nM at CB2.
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 Ki 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 Ki of 1.2 nM at CB1 and 5.3 nM at CB2.
AM-855 (part of the AM cannabinoid series) is an analgesic drug which is a cannabinoid agonist. It is a derivative of Δ8Tetrahydrocannabinol with a conformationally restricted side chain which has been bound into a fourth ring fused to the aromatic A-ring of the cannabinoid skeleton. AM-855 is an agonist at both CB1 and CB2 with moderate selectivity for CB1, with a Ki of 22.3 nM at CB1 and 58.6 nM at CB2.
AMG-1 (part of the AM cannabinoid series) is an analgesic drug which is a cannabinoid agonist. It is a derivative of Δ8-THC with a rigidified and extended 3-position side chain. AMG-1 is a potent agonist at both CB1 and CB2 with moderate selectivity for CB1, with a Ki of 0.6 nM at CB1 vs 3.1 nM at CB2.
AM-919 is an analgesic drug which is a cannabinoid receptor agonist. It is a derivative of HU-210 which has been substituted with a 6β-(3-hydroxypropyl) group. This adds a "southern" aliphatic hydroxyl group to the molecule as seen in the CP-series of nonclassical cannabinoid drugs, and so AM-919 represents a hybrid structure between the classical dibenzopyran and nonclassical cannabinoid families.
AM-4030 is an analgesic drug which is a cannabinoid receptor agonist. It is a derivative of HU-210 which has been substituted with a 6β-((E)-3-hydroxyprop-1-enyl) group. This adds a "southern" aliphatic hydroxyl group to the molecule as seen in the CP-series of nonclassical cannabinoid drugs, and so AM-4030 represents a hybrid structure between the classical and nonclassical cannabinoid families, with the 6-hydroxyalkyl chain rigidified with a double bond with defined stereochemistry. This gives AM-4030 a greater degree of selectivity, so while it is still a potent agonist at both CB1 and CB2, it is reasonably selective for CB1, with a Ki of 0.7nM at CB1 and 8.6nM at CB2, a selectivity of around 12x. Resolution of the enantiomers of AM-4030 yields an even more potent compound, although with less selectivity, with the (-) enantiomer AM-4030a having a Ki of 0.6nM at CB1 and 1.1nM at CB2.
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.
JWH-167 (1-pentyl-3-(phenylacetyl)indole) is a synthetic cannabinoid from the phenylacetylindole family, which acts as a cannabinoid agonist with about 1.75 times selectivity for CB1 with a Ki of 90 nM ± 17 and 159 nM ± 14 at CB2. Similar to the related 2'-methoxy compound JWH-250, and the 2'-chloro compound JWH-203, JWH-167 has a phenylacetyl group in place of the naphthoyl ring used in most aminoalkylindole cannabinoid compounds.
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 Ki 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.
AM-1221 is a drug that acts as a potent and selective agonist for the cannabinoid receptor CB2, with a Ki 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 Ki 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 Ki 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.
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.
Arachidonylcyclopropylamide (ACPA) is a synthetic agonist of the cannabinoid receptor 1 (CB1R). ACPA is considered to be a selective cannabinoid agonist as it binds primarily to the CB1R and has low affinity to the cannabinoid receptor 2 (CB2R).
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 effect 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 Ki 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.
PSB-SB-1202 is a coumarin derivative which is an agonist at the cannabinoid receptors CB1 and CB2, with a CB1 Ki of 32nM and a CB2 Ki of 49nM. It is also a weak antagonist at the related receptor GPR55, with an IC50 of 6350nM, but has no significant affinity for GPR18.
