Understanding the molecular pharmacology of the serotonergic system: using fluoxetine as a model

Serotonin is a monoamine neurotransmitter that is widely distributed in the body and plays an important role in a variety of psychological and other body functions such as mood, sexual desire and function, appetite, sleep, memory and learning, temperature regulation and social behaviour. This review will assess the use of fluoxetine, one of the most commonly used selective serotonin reuptake inhibitors, as a model for understanding the molecular pharmacology of the serotoninergic system.

Seven serotonin receptor families have been discovered to date. All serotonin receptors, except 5-HT(3), are G-protein coupled, seven transmembrane receptors that activate an intracellular second messenger cascade. The 5-HT(3) receptor is a ligand-gated ion channel. Furthermore, 5-HT(1A) receptors are known as autoreceptors since their stimulation inhibits the release serotonin in nerve terminals. A transporter protein found in the plasma membrane of serotonergic neurones is responsible for the reuptake of this neurotransmitter. Selective serotonin reuptake inhibitors, such as fluoxetine, act primarily at the serotonin transporter protein and have limited, if any, reaction with other neurotransmitter systems. Selective serotonin reuptake inhibitors appear to bind with the serotonin transporter with different rates of occupancy, duration and potency.

The following review focuses on the interaction of serotonin with this membrane transporter in the body and assesses the use of fluoxetine as a reference drug in the understanding of this interaction.