Neurons GABA Norepinephrine

Hydantoins Ethotoin (Peganone) Fosphenytoin (Cerebyx) Mephenytoin (Mesantoin) Phenytoin (Dilantin) Primary effect is to stabilize membrane by blocking sodium channels in repetitive-firing neurons higher concentrations may also influence concentrations of other neurotransmitters (GABA, norepinephrine, others)... 

Following the release of dopamine, the primary mode of removal from the synapse is reuptake into the presynaptic neuron via the dopamine transporter (DAT). DAT is dependent upon the energy created by the Na+/K+ pump and is a member of the Na+/Cl -dependent plasma membrane transporter family, as are the norepinephrine and 7-aminobutyric acid (GABA) transporters. Imaging studies utilizing compounds with highly specific affinity for DAT... 

In simple terms, messages travel along neurons (nerve cells) in the form of an electrical current that moves from one end of the neuron to its opposite end. The electric current is produced by a flow of sodium ions (Na ") and potassium ions (K ) across the nerve membrane, as shown in the diagram on page 11. When the electrical current reaches the end of the neuron, it causes the release of a chemical known as a neurotransmitter. Some examples of neurotransmitters are acetylcholine, serotonin, dopamine, GABA (gamma-aminobutyric acid), and norepinephrine. 

There are more than 10 billion neurons that make up the human nervous system, and they interact with one another through neurotransmitters. Acetylcholine, a number of biogenic amines (norepinephrine, dopamine, serotonin, and in all likelihood, histamine and norepinephrine), certain amino acids and peptides, and adenosine are neurotransmitters in the central nervous system. Amino acid neurotransmitters are glutamic and aspartic acids that excite postsynaptic membrane receptors of several neurons as well as y-aminobutyric acid (GABA) and glycine, which are inhibitory neurotransmitters. Endorphins, enkephalins, and substance P are considered peptidergic transmitters. There are many compounds that imitate the action of these neurotransmitters. 

Barbiturates, benzodiazepines, and GHB affect the activity of the neurotransmitter GABA, resulting in more chloride ions entering the neuron and making it more resistant to excitation. As a consequence, the output of excitatory neurotransmitters, including norepinephrine (noradrenaline), serotonin, and dopamine, is reduced. 

Figure 6. Mechanism of serotonin-induced inhibition of firing activity of norepinephrine neurons. Serotonin increases the GABA and decrease glutamate influx into the locus coeruleus, via 5-HT2A and 5-HT1A receptor-mediated mechanisms, respectively. This increase in GABA and decrease in glutamate influx results in the inhibition of firing activity of norepinephrine neurons. Published with permission of Pierre Blier, M.D., Ph.D., University of Ottawa Institute of Mental Health Research.

Szabo, S. T. Blier, P. (2001a). Serotonin (1A) receptor ligands act on norepinephrine neuron firing through excitatory amino acid and GABA(A) receptors A microiontophoretic study in the rat locus coeruleus. Synapse, 42, 203-212. 

Uptake of amine NTs from the neuronal cytosol into synaptic vesicles is achieved by vesicular monoamine transporters (VMAT1 and VMAT2) that sequester dopamine, epinephrine, norepinephrine and serotonin. A similar vesicle transporter (VGAT) sequesters GABA and glycine and a vesicular transporter (VAChT) sequesters acetylcholine into synaptic vesicles. 

The neurotransmitter phenotype, (i.e., what type of neurotransmitter is stored and ultimately will be released from the synaptic bouton) is determined by the identity of the neurotransmitter transporter that resides on the synaptic vesicle membrane. Although some exceptions to the rule may exist all synaptic vesicles of a given neuron normally will express only one transporter type and thus will have a dehned neurotransmitter phenotype (this concept is enveloped in what is known as Dale s principle see also Reference 19). To date, four major vesicular transporter systems have been characterized that support synaptic vesicle uptake of glutamate (VGLUT 1-3), GABA and glycine (VGAT), acetylcholine (VAChT), and monoamines such as dopamine, norepinephrine, and serotonin (VMAT 1 and 2). Vesicles that store and release neuropeptides do not have specific transporters to load and concentrate the peptides but, instead, are formed with the peptides already contained within. 

Skeletal muscles are controlled by large nerves in the spinal cord. The nerve cell or neuron is part of the spinal cord, but its projections, the axon and the many dendrites course outward to connect to muscle cells. The nerve axon is a sensory device that senses the muscle cells current condition. The dendrites are motor fibers that deliver the instructions to change its state to the muscle fiber. The area at which the muscle and nerve connect is called the neuromuscular junction. It is here that the end releases a chemical called a neurotransmit-ter that crosses the microscopic space between the nerve and muscle and causes the desired response. Five such neurotransmitters have been described acetylcholine, serotonin, norepinephrine, glycine, and gamma-ammi-nobutyric acid or GABA. Of these, the functions of three are known. Acetylcholine excites muscle activity and glycine and GABA inhibit it. 

---