Current therapy of mood disorders has several limitations. Although a high number of drugs are clinically available, as of today, nearly two-thirds of individuals do not achieve full symptomatic remission after treatment with conventional antidepressants. Moreover, several weeks of drug treatment are usually required to obtain clinical effects, a limitation that has considerable clinical implications, ranging from high suicide risk to reduced compliance. The characteristic lag time in classical antidepressant effectiveness has given great impulse to the search for novel therapeutics with more rapid effects. l-acetylcarnitine (LAC), a small molecule of growing interest for its pharmacological properties, is currently marketed for treatment of neuropathic pain. Recent preclinical and clinical data suggested that LAC may exert antidepressant effects with a more rapid onset than conventional drugs. Herein, we review data supporting LAC antidepressant activity and its distinctive mechanisms of action compared with monoaminergic antidepressants. Furthermore, we discuss the unique pharmacological properties of LAC that allow us to look at this molecule as representative of next generation antidepressants with a safe profile.
Keywords: ">l-acetylcarnitine; NF-κB; acetylation; adult neurogenesis; antidepressant; chronic pain; epigenetics; mGlu2; mood disorders.