Trifluoromethoxyl substituted phenylethylene diamines as high affinity sigma receptor ligands with potent anti-cocaine actions.

The phenylethylene diamines are a class of sigma receptor ligands with excellent selectivity over other biological systems and with anti-cocaine actions that involve antagonism of sigma(1) receptors. In order to increase the potency of the aromatic methoxyl substituted analogues, trifluoromethoxyl groups were introduced to prevent metabolic demethylation. The para-substituted trifluoromethoxyl substituted analogues were shown to have increased sigma receptor affinity and represent the most potent anti-cocaine phenylethylene diamines yet described.