Keywords AbstractObjectives 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. Key findings Seven serotonin receptor families have been discovered to date. All serotonin receptors, except 5-HT3, are G-protein coupled, seven transmembrane receptors that activate an intracellular second messenger cascade. The 5-HT3 receptor is a ligand-gated ion channel. Furthermore, 5-HT1A 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. Summary 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.

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Aims:A novel robust chiral gas chromatographic/mass spectrometric (GC/MS) method for the separation and measurement of fluoxetine and norfluoxetine enantiomers in urine and plasma was developed.Materials and Methods:The drug was extracted from the samples by a liquid–liquid technique, using chloroform, and the enantiomers were separated and measured on a chiral gas chromatographic column (HYDRODEX β-6TBDM®, 0.25 μm × 0.25 mm × 50 m). GC/MS instrumentation was used for the acquisition of data in the electron impact selective-ion monitoring mode.Results:The ions chosen were of a mass-to-charge ratio (m/z) exactly equal to 44 units, in order to measure fluoxetine enantiomers, 134 units in order to measure norfluoxetine enantiomers, and 58 units in order to measure diphenhydramine, the internal standard. The method was found to be linear and reproducible in the 50–500 ng/mL concentration range for both urine samples and plasma samples and for both fluoxetine and norfluoxetine, with correlation coefficients ranging between 0.994 and 0.997.Conclusions:This methodology has an enormous potential for application in pharmacokinetic studies of the enantiomers of fluoxetine