Specific modulation of sigma binding sites by the anxiolytic drug opipramol.

The atypical anxiolytic and antidepressive drug opipramol binds with high affinity to sigma1 and somewhat lower affinity to sigma2 sites. After subchronic treatment, opipramol significantly down-regulated sigma2 but not sigma1 sites. This effect was not seen for imipramine, citalopram, and reboxetine under similar conditions. On the other hand, only imipramine reduced the number of sigma1 sites. It is suggested that effects at sigma2 sites are involved in the anxiolytic properties of opipramol.