JWH-018 (1-pentyl-3-(1-naphthoyl)indole, NA-PIMO 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-015 is a chemical from the naphthoylindole family that acts as a subtype-selective cannabinoid agonist. Its affinity for CB2 receptors is 13.8 nM, while its affinity for CB1 is 383 nM, meaning that it binds almost 28 times more strongly to CB2 than to CB1. However, it still displays some CB1 activity, and in some model systems can be very potent and efficacious at activating CB1 receptors, and therefore it is not as selective as newer drugs such as JWH-133. It has been shown to possess immunomodulatory effects, and CB2 agonists may be useful in the treatment of pain and inflammation. It was discovered and named after John W. Huffman.
Synthetic cannabinoids are a class of designer drug molecules that bind to the same receptors to which cannabinoids in cannabis plants attach. These novel psychoactive substances should not be confused with synthetic phytocannabinoids or synthetic endocannabinoids from which they are in many aspects distinct.
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-019 is an analgesic chemical from the naphthoylindole family that acts as a cannabinoid agonist at both the CB1 and CB2 receptors. It is the N-hexyl homolog of the more common synthetic cannabinoid compound JWH-018. Unlike the butyl homolog JWH-073, which is several times weaker than JWH-018, the hexyl homolog is only slightly less potent, although extending the chain one carbon longer to the heptyl homolog JWH-020 results in dramatic loss of activity. These results show that the optimum side chain length for CB1 binding in the naphthoylindole series is the five-carbon pentyl chain, shorter than in the classical cannabinoids where a seven-carbon heptyl chain produces the most potent compounds. This difference is thought to reflect a slightly different binding conformation adopted by the naphthoylindole compounds as compared to the classical cannabinoids, and may be useful in characterizing the active site of the CB1 and CB2 receptors.
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-2233 is a drug that acts as a highly potent full agonist for the cannabinoid receptors, with a Ki of 1.8 nM at CB1 and 2.2 nM at CB2 as the active (R) enantiomer. It was developed as a selective radioligand for the cannabinoid receptors and has been used as its 131I derivative for mapping the distribution of the CB1 receptor in the brain. AM-2233 was found to fully substitute for THC in rats, with a potency lower than that of JWH-018 but higher than WIN 55,212-2.
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 6.9x higher than rat CB1 receptors.
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.
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. It is a full agonist at CB1 with an EC50 of 142 nM and Ki of 3.24 nM (compared to the Ki of Δ9-THC at 28.35 nM and JWH-018 at 9.62 nM), while at CB2 it acts as a partial agonist with an EC50 of 141 nM and Ki of 1.68 nM (compared to the Ki of Δ9-THC at 37.82 nM and JWH-018 at 8.55 nM). Its pharmacological characterization has also been reported in a discontinued patent application. 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, 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.
EAM-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 Japan in July 2012 as an ingredient in synthetic cannabis smoking blends Like the closely related MAM-2201 which had been first reported around a year earlier, EAM-2201 thus appears to be another novel compound invented by designer drug suppliers specifically for recreational use. Structurally, EAM-2201 is a hybrid of two known cannabinoid compounds JWH-210 and AM-2201, both of which had previously been used as active ingredients in synthetic cannabis blends before being banned in many countries.
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.
AB-CHMINACA is an indazole-based synthetic cannabinoid. It is a potent agonist of the CB1 receptor (Ki = 0.78 nM) and CB2 receptor (Ki = 0.45 nM) and fully substitutes for Δ9-THC in rat discrimination studies, while being 16x more potent. Continuing the trend seen in other cannabinoids of this generation, such as AB-FUBINACA and AB-PINACA, it contains a valine amino acid amide residue as part of its structure, where older cannabinoids contained a naphthyl or adamantane residue.
THJ-2201 is an indazole-based synthetic cannabinoid that presumably acts as a potent agonist of the CB1 receptor and has been sold online as a designer drug.
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.
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.
