Cheerful news for antidepressant research

Two research groups have independently reported new findings on the mechanism of action of an important class of antidepressant drugs. The work provides key insights into how tricyclic antidepressants interfere with neurophysiology at the molecular scale, and could eventually open the way to the development of more efficient therapies.

Tricyclic antidepressants (TCAs) are molecules that resemble a kite, with a central seven-membered ring trailing a short tail and flanked by two benzene rings. TCAs work by inhibiting neurons from taking up the monoamine neurotransmitters serotonin, norepinephrine and dopamine, which regulate mood. By blocking the re-uptake of these transmitters by their specific transporter proteins, the transmitter molecules remain in circulation for longer, prolonging their action.

However, the precise way in which the drugs work had remained unresolved. Now, Maarten Reith, Da-Neng Wang and colleagues1 at the New York University School of Medicine, US, and a team led by Eric Gouaux2 at the Oregon Health and Science University, US, have independently provided data on how TCA molecules bind to a bacterial analogue of a mammalian neurotransmitter transporter.

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