Brainstorms March 15, 2003

Neurotransmission of Cognition, Part 3. Mechanism of Action of Selective NRIs: Both Dopamine and Norepinephrine Increase in Prefrontal Cortex

Stephen M. Stahl, MD, PhD

J Clin Psychiatry 2003;64(3):230-231

Article Abstract
Brainstorms: Neurotransmission of Cognition, Part 3. Mechanism of Action of Selective NRIs: Both Dopamine and Norepinephrine Increase in Prefrontal Cortex.

New discoveries about how dopamine and norepinephrine are regulated in the prefrontal cortex (PFC) run counter to classical pharmacologic expectations of how these neurotransmitters act in the rest of the brain. In the PFC, dopamine reuptake inhibitors do not increase dopamine, but norepinephrine reuptake inhibitors (NRIs) do. The nature of counterintuitive findings like these can be initially confusing, but when understood, they are striking and can lead to a paradigm shift in the way in which psychopharmacology is applied to develop novel treatments. Just such a situation is the case for the new selective NRI atomoxetine.