AM-2233

{{Short description|Chemical compound}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 456506144

| IUPAC_name = 1-[(N-methylpiperidin-2-yl)methyl]-3-(2-iodobenzoyl)indole

| image = AM-2233_structure.png

| image_class = skin-invert-image

| width = 200

| tradename =

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| legal_AU =

| legal_CA = Schedule II

| legal_DE = Anlage II

| legal_UK = Class B

| legal_US =

| legal_NZ = Temporary Class

| legal_status =

| routes_of_administration =

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 444912-75-8

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = Z489688DK3

| ATC_prefix =

| ATC_suffix =

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 364266

| PubChem = 10226340

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 8401830

| C=22 | H=23 | I=1 | N=2 | O=1

| smiles = Ic3ccccc3C(=O)c1cn(CC2CCCCN2C)c4c1cccc4

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C22H23IN2O/c1-24-13-7-6-8-16(24)14-25-15-19(17-9-3-5-12-21(17)25)22(26)18-10-2-4-11-20(18)23/h2-5,9-12,15-16H,6-8,13-14H2,1H3

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = KSLCYQTUSSEGPT-UHFFFAOYSA-N

}}

AM-2233 is a drug that acts as a highly potent full agonist for the cannabinoid receptors, with a K_i of 1.8 nM at CB₁ and 2.2 nM at CB₂ as the active (R) enantiomer.{{Cite thesis |type=PhD Dissertation |title=Design and synthesis of selective cannabinoid receptor ligands: Aminoalkylindole and other heterocyclic analogs |author = Hongfeng Deng |year=2000 |publisher=University of Connecticut |id={{ProQuest|304624325}} }} 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.{{cite journal | vauthors = Deng H, Gifford AN, Zvonok AM, Cui G, Li X, Fan P, Deschamps JR, Flippen-Anderson JL, Gatley SJ, Makriyannis A | display-authors = 6 | title = Potent cannabinergic indole analogues as radioiodinatable brain imaging agents for the CB1 cannabinoid receptor | journal = Journal of Medicinal Chemistry | volume = 48 | issue = 20 | pages = 6386–6392 | date = October 2005 | pmid = 16190764 | doi = 10.1021/jm050135l }}{{Cite book | vauthors = Hanuš LR, Mechoulam R | title = Cannabinoids as Therapeutics | doi = 10.1007/3-7643-7358-X_2 | pages = 23–46 | year = 2005 | chapter = Cannabinoid chemistry: an overview | series = Milestones in Drug Therapy MDT | isbn = 978-3-7643-7055-8 }}{{cite journal | vauthors = Shen CP, Xiao JC, Armstrong H, Hagmann W, Fong TM | title = F200A substitution in the third transmembrane helix of human cannabinoid CB1 receptor converts AM2233 from receptor agonist to inverse agonist | journal = European Journal of Pharmacology | volume = 531 | issue = 1–3 | pages = 41–46 | date = February 2006 | pmid = 16438957 | doi = 10.1016/j.ejphar.2005.12.026 }}{{cite journal | vauthors = Dhawan J, Deng H, Gatley SJ, Makriyannis A, Akinfeleye T, Bruneus M, Dimaio AA, Gifford AN | display-authors = 6 | title = Evaluation of the in vivo receptor occupancy for the behavioral effects of cannabinoids using a radiolabeled cannabinoid receptor agonist, R-[125/131I]AM2233 | journal = Synapse | volume = 60 | issue = 2 | pages = 93–101 | date = August 2006 | pmid = 16715483 | doi = 10.1002/syn.20277 | s2cid = 21269336 | author-link4 = Alexandros Makriyannis }}

{{cite journal | vauthors = Leung K | title = R-2-[131I]Iodophenyl-(1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl)methanone | journal = Molecular Imaging and Contrast Agent Database (MICAD) [Internet] | date = Dec 12, 2006 | pmid = 20641836 }}{{cite journal | vauthors = Pei Y, Mercier RW, Anday JK, Thakur GA, Zvonok AM, Hurst D, Reggio PH, Janero DR, Makriyannis A | display-authors = 6 | title = Ligand-binding architecture of human CB2 cannabinoid receptor: evidence for receptor subtype-specific binding motif and modeling GPCR activation | journal = Chemistry & Biology | volume = 15 | issue = 11 | pages = 1207–1219 | date = November 2008 | pmid = 19022181 | pmc = 3700404 | doi = 10.1016/j.chembiol.2008.10.011 }}

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.{{cite journal | vauthors = Järbe TU, Deng H, Vadivel SK, Makriyannis A | title = Cannabinergic aminoalkylindoles, including AM678=JWH018 found in 'Spice', examined using drug (Δ(9)-tetrahydrocannabinol) discrimination for rats | journal = Behavioural Pharmacology | volume = 22 | issue = 5–6 | pages = 498–507 | date = September 2011 | pmid = 21836461 | pmc = 3212432 | doi = 10.1097/FBP.0b013e328349fbd5 }}

It is notable for inducing tinnitus,{{cite web | url=http://hamiltonmorris.blogspot.com/2014/09/am-2233-induced-tinnitus-collected.html | title=AM-2233 INDUCED TINNITUS: COLLECTED REPORTS | date=30 September 2014 | language=en | access-date=5 April 2019}} though the reasons for this are unclear and may provide valuable insight into tinnitus research.