APICA (synthetic cannabinoid drug)

This article is about the cannabinoid drug. For the metabotropic glutamate receptor antagonist, see 1-Amino-5-phosphonoindan-1-carboxylic acid.
APICA (synthetic cannabinoid drug)
Legal status
Legal status
Identifiers
  • N-(1-Adamantyl)-1-pentylindole-3-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC24H32N2O
Molar mass364.533 g·mol−1
3D model (JSmol)
  • CCCCCn1cc(C(=O)NC23CC4CC(CC(C4)C2)C3)c5ccccc15
  • InChI=1S/C24H32N2O/c1-2-3-6-9-26-16-21(20-7-4-5-8-22(20)26)23(27)25-24-13-17-10-18(14-24)12-19(11-17)15-24/h4-5,7-8,16-19H,2-3,6,9-15H2,1H3,(H,25,27)
  • Key:MDJYHWLDDJBTMX-UHFFFAOYSA-N

APICA (2NE1, SDB-001, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide) is an indole based drug that acts as a potent agonist for the cannabinoid receptors.[1]

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 its indazole derivative APINACA (sold as "AKB48").[2]

Structurally it closely resembles cannabinoid compounds from patent WO 2003/035005 but with an indole core instead of indazole, and a simple pentyl chain on the indole 1-position. Given the known metabolic liberation (and presence as an impurity) of amantadine in the related compound APINACA, it is suspected that metabolic hydrolysis of the amide group of APICA may also release amantadine.

Pharmacological testing determined APICA to have an IC50 of 175 nM at CB1, only slightly less potent than JWH-018 which had an IC50 of 169 nM, but over four times more tightly binding than APINACA, which had an IC50 of 824 nM.[3] The first published synthesis and pharmacological evaluation of APICA revealed that it acts as a full agonist at CB1 (EC50 = 34 nM) and CB2 receptors (EC50 = 29 nM).[4] Furthermore, APICA possesses cannabis-like effects in rats, and appears to be less potent than JWH-018 but more potent than THC.[4][5]

  1. ^ Cannizzaro C, Malta G, Argo A, Brancato A, Roda G, Casagni E, et al. (August 2016). "Behavioural and pharmacological characterization of a novel cannabinomimetic adamantane-derived indole, APICA, and considerations on the possible misuse as a psychotropic spice abuse, in C57bl/6J mice" (PDF). Forensic Science International. 265: 6–12. doi:10.1016/j.forsciint.2015.12.035. hdl:2434/422068. PMID 26826846.
  2. ^ Uchiyama N, Kawamura M, Kikura-Hanajiri R, Goda Y (2012). "Identification of two new-type synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA), and detection of five synthetic cannabinoids, AM-1220, AM-2233, AM-1241, CB-13 (CRA-13), and AM-1248, as designer drugs in illegal products". Forensic Toxicology. 30 (2): 114–125. doi:10.1007/s11419-012-0136-7. S2CID 44193953.
  3. ^ Uchiyama N, Kawamura M, Kikura-Hanajiri R, Goda Y (April 2013). "URB-754: a new class of designer drug and 12 synthetic cannabinoids detected in illegal products". Forensic Science International. 227 (1–3): 21–32. doi:10.1016/j.forsciint.2012.08.047. PMID 23063179.
  4. ^ a b Banister SD, Wilkinson SM, Longworth M, Stuart J, Apetz N, English K, et al. (July 2013). "The synthesis and pharmacological evaluation of adamantane-derived indoles: cannabimimetic drugs of abuse". ACS Chemical Neuroscience. 4 (7): 1081–92. doi:10.1021/cn400035r. PMC 3715837. PMID 23551277.
  5. ^ Banister SD, Stuart J, Kevin RC, Edington A, Longworth M, Wilkinson SM, et al. (August 2015). "Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135". ACS Chemical Neuroscience. 6 (8): 1445–58. doi:10.1021/acschemneuro.5b00107. PMID 25921407.