Excitatory Amino Acid Neurotransmitters Glutamate

N-MeUiyl-D-aspartate a-Amjno-3-hydroxy-4-isoxazole ptopianic acid 

The majority of NMDA agonists are closely related to the structure of glutamic acid. Thus, 4-methylene-L-glutamic acid (4.211) is a potent NMDA agonist. Bioisosteric replacement of a carboxylate group also produces agonists D,L-(tetrazol-5-yl)glycine (4.212), in which a tetrazole bioisostere replaces a carboxylate, is a potent NMDA 

3 The Clinical-Molecular Interface Stroke as a Glutamatergic Disorder 

Stroke is a leading cause of death and disability and is the most common neurological disorder of the elderly. A stroke is defined as the acute onset of a neurologic deficit (e.g., paralysis of motor movement in the arm and leg on the same side of the body— hemiplegia) associated with an abrupt alteration in blood supply to a discrete region of 

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Ketamine, a non-opioid, inhibits the excitatory effects of the endogenous excitatory amino acid neurotransmitter glutamate upon the NMDA receptor. The NMDA receptor plays a key role in the development of sensitization, hyperalgesia, and tolerance to the analgesic effects of opioids, as well as in certain preclinical models of neurotoxicity. We have demonstrated that... 

Opioids also interact with excitatory amino acid neurotransmitters. At lower micromolar concentrations, p agonists (e.g., DAMGO) enhance NMDA activity in the nucleus accumbens, but inhibit non-NMDA activity (Martin et al. 1997). At higher concentrations (5 pM), NMDA currents are reduced. Conversely, central administration of glutamate can precipitate a withdrawal syndrome in morphine-dependent animals, similar to the opioid antagonist naloxone. NMDA mechanisms also appear to be involved in the development of morphine tolerance. Competitive and noncompetitive NMDA antagonists and inhibitors of nitric oxide synthase reduce or eliminate tolerance to morphine (Elliott et al. 1995 Bilsky et al. 1996). However, this does not occur for tolerance to k opioids. Pharmacokinetics... 

Glutamate is the main excitatory amino acid neurotransmitter in central and peripheral nervous systems. Its concentration in brain is higher than in other body tissues. In the brain, the concentration of glutamate is 3- to 4-fold greater than that of aspartate, taurine, or glutamine (McGeer et al., 1987). The most abundant amino acid... 

Ketamine exerts its physiological effects at the molecular level by interfering with the actions of excitatory amino acid neurotransmitters, primarily glutamate, the most prevalent excitatory neurotransmitter in the brain. The excitatory neurotransmitters regulate numerous functions of the central nervous system. 

Another important family of ligand gated ion channels is the receptors for the excitatory amino acid neurotransmitters such as glutamate and aspartate (Figure 10.8). These act as neurotransmitters at the vast majority of excitatory synapses in the brain. These receptors are also multisubunit ion channel arrays, in this case consisting of tetramers of related subunits (Wolhnuth and Sobolevsky, 2004). The proteins that make up these subunits are all related in structure but are quite different from those that make up the nicotinic and GABA-A receptor family. 

Glutamate An excitatory amino acid neurotransmitter (Chapter 3). 

Glutamate is the major excitatory neuro transmitter in the cortex and hippocampus. Many neuronal pathways essential to learning and memory use glutamate as a neurotransmitter, including the pyramidal neurons (a layer of neurons with long axons carrying information out of the cortex), hippocampus, and entorhinal cortex. Glutamate and other excitatory amino acid neurotransmitters have been implicated as... 

The amino acid neurotransmitters are subdivided into primarily excitatory (glutamate, aspartate) and inhibitory (y-aminobutyric acid, GABA, glycine) types. 

The excitatoiy amino acids (EAA), glutamate and aspartate, are the principal excitatory neurotransmitters in the brain. They are released by neurons in several distinct anatomical pathways, such as corticofugal projections, but their distribution is practically ubiquitous in the central nervous system. There are both metabotropic and ionotropic EAA receptors. The metabotropic receptors bind glutamate and are labeled mGluRl to mGluRB. They are coupled via G-proteins to phosphoinositide hydrolysis, phospholipase D, and cAMP production. Ionotropic EAA receptors have been divided into three subtypes /V-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA), and kainate receptors (Nakanishi 1992). 

Excitatory amino acids Ibotenic acid is structurally related to glutamate, the principal excitatory neurotransmitter, and it activates NMDA receptors (Madsen et al. 1990 Mayer and Westbrook 1987 Schwarcz et al. 1979 Honore et al. 1981). 

There is now evidence that the mammalian central nervous system contains several dozen neurotransmitters such as acetylcholine, noradrenaline, dopamine and 5-hydroxytryptamine (5-HT), together with many more co-transmitters, which are mainly small peptides such as met-enkephalin and neuromodulators such as the prostaglandins. It is well established that any one nerve cell may be influenced by more than one of these transmitters at any time. If, for example, the inhibitory amino acids (GABA or glycine) activate a cell membrane then the activity of the membrane will be depressed, whereas if the excitatory amino acid glutamate activates the nerve membrane, activity will be increased. The final response of the nerve cell that receives all this information will thus depend on the balance between the various stimuli that impinge upon it. 

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