Gamma-aminobutyric acid, serotonin, dopamine, and norepinephrine receptors and transporters

The GABA, serotonin, dopamine, and norepinephrine receptors and transporters represent the primary mediators of chemical signaling in the mammalian central nervous system [1]. The GABAergic system, primarily through GABA-A and GABA-B receptors, provides the main inhibitory tone, while the monoamines (serotonin, dopamine, and norepinephrine) modulate mood, reward, and arousal [2]. Transporters such as the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET) are critical for terminating synaptic signals by resequestering neurotransmitters into the presynaptic neuron [3]. Dysfunction in these systems is a hallmark of psychiatric conditions like depression and anxiety, as well as neurological disorders like Parkinson's disease [4]. Therapeutic agents targeting these proteins include selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, and antipsychotics, which work by altering synaptic concentrations or receptor activity [5]. These targets are often classified as G protein-coupled receptors, ligand-gated ion channels, or solute carrier transporters [1, 3]. Clinical management of these targets requires careful titration to avoid adverse effects like serotonin syndrome or extrapyramidal symptoms [5]. Biomarkers for these systems include PET imaging of transporter occupancy and measurement of neurotransmitter metabolites in cerebrospinal fluid [6].

Other names

Monoamine and GABA systemsNeurotransmitter receptors and transportersBiogenic amine receptors and transporters

The mechanism of action involves the modulation of synaptic neurotransmission through the inhibition of neurotransmitter reuptake by transporters (e.g., SERT, DAT, NET), the activation or blockade of G protein-coupled receptors (e.g., 5-HT, DA, and NE receptors), and the allosteric modulation of ligand-gated ion channels (e.g., GABA-A receptors) [1, 3, 5].