Nortriptyline

Nortriptyline is a tricyclic antidepressant with actions and uses similar to these of amitriptyline. It is the principal active metabolite of amitriptyline.

Parts of metabolism of Nortriptyline include hydroxylation (possibly to active metabolites). N-oxidation and conjugation with glucuronic acid. Nortriptyline is widely distributed throughout the body and is extensively bound to plasma and tissue protein. Plasma concentrations of Nortriptyline vary very widely between individuals and no simple correlation with therapeutic response has been established.

Nortriptyline inhibits ion channels, which are responsible for cardiac conduction (SCN5A- and hERG channels), in the upper micromolar range of therapeutic plasma concentrations. Therefore, nortriptyline may increase the risk for cardiac arrhythmia.

Nortriptyline did not show any mutagenic potential.

The reproductive toxicity of nortriptyline has not been investigated in animals. For its parent substance amitriptyline, teratogenic effects and developmental delays, such as cranial malformations and encephalocele, have been only observed at high dosages. There was also a possible association with an effect on fertility in rats, namely a lower pregnancy rate. The reason for the effect on fertility is unknown.