Yohimbine derivatives are disclosed having modification of the C-16 carboxyl group to include a sidechain and where the resulting derivative does not possess a second yohimbine pharmacophore (i.e., the compound is not a yohimbine dimer). The yohimbine derivatives of the present invention are preferably characterized by selective activity as .alpha..sub.2c-AR antagonists. Use of the compounds, or pharmaceutical composition containing them, for treating or preventing an .alpha..sub.2c adrenergic receptor mediated condition or disorder, and for antagonizing activity of an .alpha..sub.2c adrenergic receptor are also disclosed.