Doxepin is a mixture of ("E") and ("Z") stereoisomers with an approximate ratio of 85:15. When doxepin was developed, no effort was made to separate or balance the mixture following its synthesis, resulting in the asymmetric ratio. ("Z")-Doxepin is more active as an inhibitor of serotonin and norepinephrine reuptake than ("E")-doxepin. The selectivity of doxepin for inhibition of norepinephrine reuptake over that of serotonin is likely due to the 85% presence of ("E")-doxepin in the mixture. Most other tertiary amine TCAs like amitriptyline and imipramine do not exhibit "E"-"Z" isomerism or such mixture asymmetry and are comparatively more balanced inhibitors of serotonin and norepinephrine reuptake.