Tricyclic antidepressants undergo biotransformation in the liver with CYP2D6 catalyzing hydroxylation, whereas CYP2C19 mediates demethylation of the parent drug. The demethylated metabolites are partially tricyclic drugs by themselves, such as nortriptyline and desipramine, which are demethyl-metabolites of amitriptyline and imipramine. It is unknown whether the analgesic effect of amitriptyline is mediated through its precursor or the metabolites.