03.01.5.2 Inhibition of the Serotonin Transporter

An important group of drugs that inhibit transporters are the antidepressants. The biochemical cause of depression may be abnormal function of the neurotransmitters in the brain. One of the main neurotransmitters implicated in depression is 5-hydroxytryptamine (5-HT), which is also known as serotonin. One thing we do know about depression is that there is long-term effectiveness in depression of drugs that increase the levels of 5-HT in the brain. Inhibitors of the 5-HT transporter increase the levels of 5-HT in the synapses of the brain.

To understand how this works, we first need to review the physiological process. On activation of the nerve terminal, 5-HT is released, and then stimulates 5-HT receptors to have an effect (Figure 3.14).

Figure 3.14 SERT transporter (Copyright QUT University, Sheila Doggrell)

The action of 5-HT is short lived, as it is rapidly inactivated. The 5-hydroxytryptamine (5-HT) is inactivated by transport back into the neurone, on a transporter that is selective for 5-HT, the SERT (the SERotonin Transporter). When it is stored in nerve endings, with no access to its receptors, the 5-HT is inactive. SERT is inhibited by Prozac (Fluoxetine). This inhibits inactivation of 5-HT, and increases the levels of 5-HT in the synapse, with increased stimulation of receptor, and an increased effect. It takes a bit of time, but eventually raising the levels of 5-HT in the brain synapses has an antidepressant effect.