The article reviews recent progress in the understanding of neurotransmitter transporters, focusing on their role in synaptic signal termination and their pharmacological significance. It highlights the importance of these transporters in drug action, particularly for antidepressants and stimulants like cocaine. The review covers the history of the discovery of neurotransmitter uptake systems, the molecular biology of these transporters, and their regulation. Key points include: 1. **Neurotransmitter Uptake as Signal Termination**: Transporters are crucial for terminating synaptic transmission by reuptaking released neurotransmitters. This process is facilitated by sodium-dependent cotransport systems, which use the energy stored in transmembrane electrochemical gradients. 2. **Transporter Cloning and Characterization**: Recent advances in molecular biology have led to the cloning of various neurotransmitter transporters, including those for norepinephrine, dopamine, and serotonin. These studies have provided insights into their structure and function, revealing common motifs and differences among them. 3. **Pharmacological and Functional Properties**: Transporters exhibit specific substrate preferences and are influenced by various ligands and conditions. For example, antidepressants like fluoxetine and imipramine are known to block serotonin and norepinephrine transporters, respectively. 4. **Regulation of Transporters**: Transporters can be regulated by second messengers, such as calcium and arachidonic acid, and by transmembrane electrochemical gradients. Additionally, their activity can be modulated by phosphorylation and subcellular redistribution. 5. **Clinical Implications**: The understanding of neurotransmitter transporters has implications for the development of therapeutic drugs, particularly those targeting neurotransmitter systems involved in mental disorders. The article emphasizes the importance of these transporters in both physiological and pathological processes, highlighting the need for further research to fully understand their roles and potential therapeutic applications.The article reviews recent progress in the understanding of neurotransmitter transporters, focusing on their role in synaptic signal termination and their pharmacological significance. It highlights the importance of these transporters in drug action, particularly for antidepressants and stimulants like cocaine. The review covers the history of the discovery of neurotransmitter uptake systems, the molecular biology of these transporters, and their regulation. Key points include: 1. **Neurotransmitter Uptake as Signal Termination**: Transporters are crucial for terminating synaptic transmission by reuptaking released neurotransmitters. This process is facilitated by sodium-dependent cotransport systems, which use the energy stored in transmembrane electrochemical gradients. 2. **Transporter Cloning and Characterization**: Recent advances in molecular biology have led to the cloning of various neurotransmitter transporters, including those for norepinephrine, dopamine, and serotonin. These studies have provided insights into their structure and function, revealing common motifs and differences among them. 3. **Pharmacological and Functional Properties**: Transporters exhibit specific substrate preferences and are influenced by various ligands and conditions. For example, antidepressants like fluoxetine and imipramine are known to block serotonin and norepinephrine transporters, respectively. 4. **Regulation of Transporters**: Transporters can be regulated by second messengers, such as calcium and arachidonic acid, and by transmembrane electrochemical gradients. Additionally, their activity can be modulated by phosphorylation and subcellular redistribution. 5. **Clinical Implications**: The understanding of neurotransmitter transporters has implications for the development of therapeutic drugs, particularly those targeting neurotransmitter systems involved in mental disorders. The article emphasizes the importance of these transporters in both physiological and pathological processes, highlighting the need for further research to fully understand their roles and potential therapeutic applications.