Central nervous system excitatory

In a retrospective survey of 355 medical records of patients who received intravenous PCA pethidine between 1988 and 1994 the mean consumption by patients who had used over 600 mg/day of pethidine was 13.3 mg/ kg/day in asymptomatic patients and 16.9 mg/kg/day in the 2% of patients who presented with central nervous system excitatory signs and symptoms (muscle twitches, jitteriness, agitation, and hallucinations) (13). The authors recommended a maximum safe dose of pethidine by PCA of 10 mg/kg/day for no more than 3 days. 

Kaiko RF, Foley KM, Grabinski PY, Heidrich G, Rogers AG, Inturrisi CE, Reidenberg MM. Central nervous system excitatory effects of meperidine in cancer patients. Ann Neurol 1983 13(2) 180-5. 

Most neurons in the central nervous system are stimulated by L- glutamate, the major excitatory amino acid in the brain. The postsynaptic actions of... 

Glutamate An excitatory amino acid found in the central nervous system. 

L-Glutamate acts as an excitatory neurotransmitter at many synapses in the mammalian central nervous system. Electrophysiological measurements and the use of various selective agonists and antagonists indicate that different glutamate receptors co-exist on many neurons. 

The amino acid glutamate is the most widely used excitatory neurotransmitter in the central nervous system of mammals. Glutamate is the primary neurotransmitter used by the vast majority of reticular formation, thalamic and cortical neurons, which play a crucial role in the generation of the characteristic electrical activity as recorded in the electroencephalogram (for details see Steriade McCarley (2005)). The activity of these neurons is tightly regulated by the other neurotransmitters described in this chapter. 

Collingridge, G. L. Lester, R. A. (1989). Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol Rev. 41, 143-210. 

Monaghan, D. T., Bridges, R. J. Cotman, C. W. (1989). The excitatory amino acid receptors their classes, pharmacology and distinct properties in the function of the central nervous system. A Rev. Pharmacol Toxicol. 29, 365-402. 

V-methyl-D-aspartate receptors. Glutamate is the major excitatory neurotransmitter in the central nervous system (Ch. 15). Its receptors can be divided into three types AMPA/kainate, NMDA and metabotropic receptors. NMDA receptors are composed of two different types of subunit - NR1 and NR2. They play an important role in the induction of synaptic plasticity and excitotoxicity. 

Ionotropic glutamate receptors mediate fast excitatory neurotransmission in practically all areas of the central nervous system (CNS). They are also critical for both the induction and expression of synaptic plasticity, and have been implicated in diverse pathological conditions, such as epilepsy, ischemic brain damage, anxiety, and addiction. There are three subtypes of ionotropic glutamate receptors that are named after their high-affinity agonists as a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), N-1nethyl-D-aspartate (NMDA), and kainate (KA) receptors (1). 

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). 

Mayer ML, Westbrook GL. (1987). The physioiogy of excitatory amino acids in the vertebrate central nervous system. Prog Neurobioi. 28(3) 197-276. 

Glutamic acid also has a side chain carboxyl group that will lose a proton and become an anionic carboxylate group under physiological conditions. Glutamic acid is the most important excitatory neurotransmitter in the human central nervous system. 

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. 

Excitatory synaptic transmission in the central nervous system is largely glu-tamatergic. There is ample evidence for inhibition of excitatory transmission... 

Glutamic Acid A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. 

The classification of 5-HT-receptors is still an ongoing field of research. 5-HTi, 5-HT2, 5-HT4, 5-HTe and S-HT subtypes belong to the superfamily of G-protein coupled receptors whereas the 5-HT3 subtype is a ligand-gated ion channel. The activation of 5-HTi-receptors induces excitatory or inhibitory effects in the periphery as well as in the central nervous system. There are presynaptic 5-HTi-autoreceptors. 5-HT2-receptors in the periphery are located postsynaptieally, their stimulation induce only excitatory effects. 

Bullock R, Zauner A, Woodward J, Young HP (1995) Massive persistent release of excitatory amino acids following human occlusive stroke. Stroke 26 2187-2189 Burnashev N (1996) Calcium permeability of glutamate-gated channels in the central nervous system. Curr Opin Neurobiol 6 311-317... 

Glutamate is the major excitatory amino acid in the brain. It has a key role in learning and memory and is involved in the mediation of the response to stress. Glutamate receptors are present throughout the central nervous system but differ widely according to their localisation and function (Kent et al. 2002), and as a result have not been easy to identify as targets for pharmacological manipulation. 

Chapter 28). Stimulation of nicotinic receptors in adrenergic nerve terminals leads to the release of norepinephrine and activation of nicotinic chemoreceptors in the aortic arch and carotid bodies causes nausea and vomiting. Nicotinic receptors in the central nervous system mediate a complex range of excitatory and inhibitory effects. 

Androgens produce both virilizing and protein anabolic actions (Table 63.1). The virilizing actions of testosterone include irreversible effects that occur during em-bryogenesis, that is, those that induce differentiation of the central nervous system and male reproductive tracts, and the excitatory actions at puberty that are... 

Glutamate (Glu) is the most abundant amino acid in the central nervous system (CNS). It serves many functions as an intermediate in neuronal metabolism, e.g., as a precursor for GABA. About 30% of the total glutamate in the brain functions as the major excitatory neurotransmitter. 

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