IBOGAINE AND ITS CONGENERS ARE SIGMA(2) RECEPTOR-SELECTIVE LIGANDS WITH MODERATE AFFINITY

Ibogaine (12-methoxyibogamine) exhibited moderate affinity for sigma(2 ) sites (K-i = 201 nM) and low affinity for a, sites (K-i = 8554 nM), thus showing 43-fold selectivity for sigma(2) receptors. Tabernanthine (13-methoxyibogamine) and(+/-)-ibogamine had sigma(2) K-i = 194 nM an d 137 nM, respectively. However, they showed 3- to 5-fold higher sigma (1) affinity compared to ibogaine, resulting in about 14-fold selectiv ity for sigma(2) sites over sigma(1). A potential ibogaine metabolite, O-des-methyl-ibogaine, had markedly reduced sigma(2) affinity relativ e to ibogaine (K-i = 5,226 nM) and also lacked significant affinity fo r sigma(1) sites. (+/-)-Coronaridine ((+/-)-18-carbomethoxyibogamine) and harmaline (1-methyl-7-methoxy-3,4-dihydro-beta-carboline) lacked s ignificant affinity for either a subtype. Thus, sigma(2) receptors cou ld play a role in the actions of ibogaine.