title: Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity.
abstract: Ibogaine (12-methoxyibogamine) exhibited moderate affinity for sigma 2 sites (Ki = 201 nM) and low affinity for sigma 1 sites (Ki = 8554 nM), thus showing 43-fold selectivity for sigma 2 receptors. Tabernanthine (13-methoxyibogamine) and (+/-)-ibogamine had sigma 2 Ki = 194 nM and 137 nM, respectively. However, they showed 3- to 5-fold higher sigma 1 affinity compared to ibogaine, resulting in about 14-fold selectivity for sigma 2 sites over sigma 1. A potential ibogaine metabolite, O-des-methyl-ibogaine, had markedly reduced sigma 2 affinity relative to ibogaine (Ki = 5,226 nM) and also lacked significant affinity for sigma 1 sites. (+/-)-Coronaridine ((+/-)-18-carbomethoxyibogamine) and harmaline (1-methyl-7-methoxy-3,4-dihydro-beta-carboline) lacked significant affinity for either sigma subtype. Thus, sigma 2 receptors could play a role in the actions of ibogaine.
authors.affiliation: Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Bowen
authors.forename: B J
authors.initials: BJ
authors.lastname: Vilner
authors.forename: W
authors.initials: W
authors.lastname: Williams
authors.forename: C M
authors.initials: CM
authors.lastname: Bertha
authors.forename: M E
authors.initials: ME
authors.lastname: Kuehne
authors.forename: A E
authors.initials: AE
authors.lastname: Jacobson
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D006168:Guinea Pigs; D006213:Hallucinogens / Q000378:metabolism*; D007050:Ibogaine / Q000031:analogs & derivatives / Q000378:metabolism*; D008024:Ligands; D008099:Liver / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017480:Receptors, sigma / Q000378:metabolism*
chemical_list: D006213:Hallucinogens; D008024:Ligands; D017480:Receptors, sigma; D007050:Ibogaine