JWH-018 (1-pentyl-3-(1-naphthoyl)indole) or AM-678 is an analgesic chemical from the naphthoylindole family that acts as a full agonist at both the CB1 and CB2 cannabinoid receptors, with some selectivity for CB2. It produces effects in animals similar to those of tetrahydrocannabinol (THC), a cannabinoid naturally present in cannabis, leading to its use in synthetic cannabis products that in some countries are sold legally as "incense blends".
JWH-081 is an analgesic chemical from the naphthoylindole family, which acts as a cannabinoid agonist at both the CB1 and CB2 receptors. With a Ki of 1.2nM it is fairly selective for the CB1 subtype, its affinity at this subtype is measured at approximately 10x the affinity at CB2(12.4nM). It was discovered by and named after John W. Huffman.
JWH-073, a synthetic cannabinoid, is an analgesic chemical from the naphthoylindole family that acts as a partial agonist at both the CB1 and CB2 cannabinoid receptors. It is somewhat selective for the CB1 subtype, with affinity at this subtype approximately 5x the affinity at CB2. The abbreviation JWH stands for John W. Huffman, one of the inventors of the compound.
JWH-203 (1-pentyl-3-(2-chlorophenylacetyl)indole) is an analgesic chemical from the phenylacetylindole family that acts as a cannabinoid agonist with approximately equal affinity at both the CB1 and CB2 receptors, having a Ki of 8.0 nM at CB1 and 7.0 nM at CB2. It was originally discovered by, and named after, Dr. John W. Huffman, but has subsequently been sold without his permission as an ingredient of synthetic cannabis smoking blends. Similar to the related 2'-methoxy compound JWH-250, the 2'-bromo compound JWH-249, and the 2'-methyl compound JWH-251, JWH-203 has a phenylacetyl group in place of the naphthoyl ring used in most aminoalkylindole cannabinoid compounds, and has the strongest in vitro binding affinity for the cannabinoid receptors of any compound in the phenylacetyl group.
JWH-210 is an analgesic chemical from the naphthoylindole family, which acts as a potent cannabinoid agonist at both the CB1 and CB2 receptors, with Ki values of 0.46 nM at CB1 and 0.69 nM at CB2. It is one of the most potent 4-substituted naphthoyl derivatives in the naphthoylindole series, having a higher binding affinity (i.e. lower Ki) at CB1 than both its 4-methyl and 4-n-propyl homologues JWH-122 (CB1 Ki 0.69 nM) and JWH-182 (CB1 Ki 0.65 nM) respectively, and than the 4-methoxy compound JWH-081 (CB1 Ki 1.2 nM). It was discovered by and named after John W. Huffman.
JWH-007 is an analgesic chemical from the naphthoylindole family, which acts as a cannabinoid agonist at both the CB1 and CB2 receptors. It was first reported in 1994 by a group including the noted cannabinoid chemist John W. Huffman. It was the most active of the first group of N-alkyl naphoylindoles discovered by the team led by John W Huffman, several years after the family was initially described with the discovery of the N-morpholinylethyl compounds pravadoline (WIN 48,098), JWH-200 (WIN 55,225) and WIN 55,212-2 by the Sterling Winthrop group. Several other N-alkyl substituents were found to be active by Huffman's team including the n-butyl, n-hexyl, 2-heptyl, and cyclohexylethyl groups, but it was subsequently determined that the 2-methyl group on the indole ring is not required for CB1 binding, and tends to increase affinity for CB2 instead. Consequently, the 2-desmethyl derivative of JWH-007, JWH-018, has slightly higher binding affinity for CB1, with an optimum binding of 9.00 nM at CB1 and 2.94 nM at CB2, and JWH-007 displayed optimum binding of 9.50 nM at CB1 and 2.94 nM at CB2.
RCS-4, or 1-pentyl-3-(4-methoxybenzoyl)indole, is a synthetic cannabinoid drug sold under the names SR-19, BTM-4, or Eric-4, but originally, OBT-199.
AM-2201 is a recreational designer drug that acts as a potent but nonselective full agonist for the cannabinoid receptor. It is part of the AM series of cannabinoids discovered by Alexandros Makriyannis at Northeastern University.
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 Ki of 0.27 nM at CB1 while the (S)-enantiomer has a much weaker Ki of 217 nM.
UR-144 (TMCP-018, KM-X1, MN-001, YX-17) is a drug invented by Abbott Laboratories, that acts as a selective full agonist of the peripheral cannabinoid receptor CB2, but with much lower affinity for the psychoactive CB1 receptor.
MAM-2201 is a drug that presumably acts as a potent agonist for the cannabinoid receptors. It had never previously been reported in the scientific or patent literature, and was first identified by laboratories in the Netherlands and Germany in June 2011 as an ingredient in synthetic cannabis smoking blends. Like RCS-4 and AB-001, MAM-2201 thus appears to be a novel compound invented by "research chemical" suppliers specifically for grey-market recreational use. Structurally, MAM-2201 is a hybrid of two known cannabinoid compounds JWH-122 and AM-2201, both of which had previously been used as active ingredients in synthetic cannabis blends before being banned in many countries.
APINACA (AKB48, N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide) is a drug that acts as a reasonably potent agonist for the cannabinoid receptors, with a Ki of 304.5nM and an EC50 of 585nM at CB1. It had never previously been reported in the scientific or patent literature, and was first identified by laboratories in Japan in March 2012 as an ingredient in synthetic cannabis smoking blends, along with a related compound APICA. Structurally, it closely resembles cannabinoid compounds from a University of Connecticut patent (WO 2003/035005), but with a simple pentyl chain on the indazole 1-position, and APINACA falls within the claims of this patent despite not being disclosed as an example.
XLR-11 (5"-fluoro-UR-144 or 5F-UR-144) is a drug that acts as a potent agonist for the cannabinoid receptors CB1 and CB2 with EC50 values of 98 nM and 83 nM, respectively. It is a 3-(tetramethylcyclopropylmethanoyl)indole derivative related to compounds such as UR-144, A-796,260 and A-834,735, but it is not specifically listed in the patent or scientific literature alongside these other similar compounds, and appears to have not previously been made by Abbott Laboratories, despite falling within the claims of patent WO 2006/069196. XLR-11 was found to produce rapid, short-lived hypothermic effects in rats at doses of 3 mg/kg and 10 mg/kg, suggesting that it is of comparable potency to APICA and STS-135.
APICA is an indole based drug that acts as a potent agonist for the cannabinoid receptors.
STS-135 (N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide, also called 5F-APICA) is a designer drug offered by online vendors as a cannabimimetic agent. The structure of STS-135 appears to use an understanding of structure-activity relationships within the indole class of cannabimimetics, although its design origins are unclear. STS-135 is the terminally-fluorinated analogue of SDB-001, just as AM-2201 is the terminally-fluorinated analogue of JWH-018, and XLR-11 is the terminally-fluorinated analogue of UR-144. STS-135 acts a potent cannabinoid receptor agonist in vitro, with an EC50 of 51 nM for human CB2 receptors, and 13 nM for human CB1 receptors. STS-135 produces bradycardia and hypothermia in rats at doses of 1–10 mg/kg, suggesting cannabinoid-like activity.
PB-22 is a designer drug offered by online vendors as a cannabimimetic agent, and detected being sold in synthetic cannabis products in Japan in 2013. PB-22 represents a structurally unique synthetic cannabinoid chemotype, since it contains an ester linker at the indole 3-position, rather than the precedented ketone of JWH-018 and its analogs, or the amide of APICA and its analogs.
5F-PB-22 is a designer drug which acts as a cannabinoid agonist. The structure of 5F-PB-22 appears to have been designed with an understanding of structure–activity relationships within the indole class of cannabinoids.
5F-AMB (also known as 5F-MMB-PINACA and 5F-AMB-PINACA) is an indazole-based synthetic cannabinoid from the indazole-3-carboxamide family, which has been used as an active ingredient in synthetic cannabis products. It was first identified in Japan in early 2014. Although only very little pharmacological information about 5F-AMB itself exists, its 4-cyanobutyl analogue (instead of 5-fluoropentyl) has been reported to be a potent agonist for the CB1 receptor (KI = 0.7 nM).
NNE1 (also known as NNEI, MN-24 and AM-6527) is an indole-based synthetic cannabinoid, representing a molecular hybrid of APICA and JWH-018 that is an agonist for the cannabinoid receptors, with Ki values of 60.09 nM at CB1 and 45.298 nM at CB2 and EC50 values of 9.481 nM at CB1 and 1.008 nM at CB2. It was invented by Abbott and has a CB1 receptor pEC50 of 8.9 with around 80x selectivity over the related CB2 receptor. It is suspected that metabolic hydrolysis of the amide group of NNE1 may release 1-naphthylamine, a known carcinogen, given the known metabolic liberation (and presence as an impurity) of amantadine in the related compound APINACA, and NNE1 was banned in New Zealand in 2012 as a temporary class drug to stop it being used as an ingredient in then-legal synthetic cannabis products. NNE1 was subsequently found to be responsible for the death of a man in Japan in 2014.
FUB-PB-22 (QUFUBIC) is an indole-based synthetic cannabinoid that is a potent agonist of the CB1 receptor and has been sold online as a designer drug.
