Central nervous system transmitters

Baclofen is structurally related to gamma-aminobutyric acid (GABA), an inhibitory central nervous system transmitter it inhibits reflex activity mainly in the spinal cord. Baclofen reduces spasticity and flexor spasms, but as it has no action on voluntary muscle power, function is commonly not improved. Ambulant patients may need their leg spasticity to provide support and reduction of spasticity may expose the weakness of the limb. It benefits some cases of trigeminal neuralgia. Baclofen is given orally (tVj 3 h). 

The pharmacology of insect central nervous system transmitter receptors and their associated modulatory sites and ion channels is less thoroughly known than that of the peripheral neuromuscular systems. This is in part due to the relative inaccessibility of the central... 

CGRP is widely distributed throughout the peripheral and central nervous systems and is found ia sensory neurons and ia the autonomic and enteric nervous systems. In many iastances CGRP is co-localized with other neuroregulators, eg, ACh ia motor neurons, substance P, somatostatin, vasoactive intestinal polypeptide (VIP), and galanin ia sensory neurons. It is also present ia the CNS, with ACh ia the parabigeminal nucleus and with cholecystokinin (CCK) ia the dorsal parabrachial area. CGRP functions as a neuromodulator or co-transmitter. 

Acetylcholine (Ach) is an ester of acetic acid and choline with the chemical formula CH3COOCH2CH2N+ (CH3)3. ACh functions as a chemical transmitter in both the peripheral nervous system (PNS) and central nervous system (CNS) in a wide range of organisms, humans included. Neurotransmitter involved in behavioral state control, postural tone, cognition and memory, and autonomous parasympathetic (and preganglionic sympathetic) nervous system. 

Cholinergic Transmission is the process of synaptic transmission which uses mainly acetylcholine as a transmitter. Cholinergic transmission is found widely in the peripheral and central nervous system, where acetylcholine acts on nicotinic and muscarinic receptors. 

Enterochromaffin cells are interspersed with mucosal cells mainly in the stomach and small intestine. In the blood, serotonin is present at high concentrations in platelets, which take up serotonin from the plasma by an active transport process. Serotonin is released on platelet activation. In the central nervous system, serotonin serves as a transmitter. The main serotonin-containing neurons are those clustered in form of the Raphe nuclei. Serotonin exerts its biological effects through the activation of specific receptors. Most of them are G-protein coupled receptors (GPCRs) and belong to the 5-HTr, 5-HT2-, 5-HT4-, 5-HTs-, 5-HT6-, 5-HT7-receptor subfamilies. The 5-HT3-receptor is a ligand-operated ion channel. 

Neurohumoral transmitters are chemicals that facilitate the transmission of nerve impulses across nerve synapses and neuroeffector junctions. Acetylcholine is a neurohumoral transmitter that is present in the peripheral autonomic nervous system, in the somatic motor nervous system, and in some portions of the central nervous system. 

Russ, H, Staust, K, Martel, R, Gliess, M and Schomig, E (1996) The extracellular transporter for monoamine transmitters exists in cells derived from human central nervous system glia. Eur. J. 

Complicated processes govern wakefulness, sleep, and the transitions leading to sleep initiation and maintenance. Although the neurophysiology of sleep is complex, certain neurotransmitters promote sleep and wakefulness in different areas of the central nervous system (CNS). Serotonin is thought to control non-REM sleep, whereas cholinergic and adrenergic transmitters mediate REM sleep. Dopamine, norepinephrine, hypocretin, substance P, and histamine all play a role in wakefulness. Perturbations of various neurotransmitters are responsible for some sleep disorders and explain why various treatment modalities are beneficial. 

Many lines of evidence. .. make it seem probable that GABA is a major inhibitory transmitter in the vertebrate central nervous system . 

Catecholamines, 6 (1969) 200 Cell membrane transfer, 14(1977) 1 Central nervous system, drugs, transmitters and peptides, 23 (1986) 91 Centrally acting dopamine D2 receptor agonists, 29 (1992) 185 Chartreusin, 19 (1982) 249 Chelating agents, 20 (1983) 225... 

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. 

Substances with a neuromodulatory effect on brain neurotransmitters by direct actions of specific receptors that modify the actions of the transmitters listed include prostaglandins, adenosine, enkephalins, substance P, cholecystokinin, endorphins, endogenous benzodiazepine receptor ligands, and possibly histamine. CNS, central nervous system. NMDA, N-methyl-D-aspartate. Strych, strychnine. 

Noradrenaline is the main catecholamine in postganglionic sympathetic nerves and in the central nervous system it is also released from the adrenal gland together with adrenaline. Recently adrenaline has also been shown to be a transmitter in the hypothalamic region of the mammalian brain so, while the terms "noradrenergic" and "adrenergic" are presently used interchangeably, it is anticipated that they will be used with much more precision once the unique functions of adrenaline in the brain have been established. 

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. 

Like reserpine guanethidine interferes with the ability of vesicular transmitter storage. In contrast to reserpine, guanethidine is unable to enter the central nervous system and is therefore void of any centrally mediated side effects. 

HT3-receptors in the central nervous system are located on various types of neurons. On activation these receptors induce a release of the respective transmitter (noradrenaline, substance P). Due to this mechanism this subtype is involved in many reflex processes. 

The chemical transmitters may be small molecules— notably acetylcholine, norepinephrine, epinephrine, serotonin, dopamine, or histamine. Acetylcholine and norpeinephrine are the dominant neurotransmitters in the parasympathetic and sympathetic nervous systems, respectively. Dopamine and serotonin are employed primarily in the central nervous system. Neurotransmitters may also be more complex peptides (small proteins) such as substance P, vasopressin, endorphins, and enkephalins. The latter agents are of particular importance to our considerations of opium since they represent the endogenous opiates—agents that exist within the body whose actions are mimicked by exogenous, or outside, agents such as morphine, heroin, codeine, and so on. These neurotransmitters serve to convey information between neurons across the synaptic cleft (the junction where two neurons meet) or at the neuroeffector junction (the site between neuron and an innervated organ such as muscle or secretory gland). 

Each neuron has specific synthetic machinery that enables it to both synthesize and eliminate a specific neurotransmitter. For example, neurons of the sympathetic nervous system employ norepinephrine and epinephrine as their transmitters. Other neurons, particularly in the central nervous system, employ dopamine as their transmitter. Dopamine is a particularly important transmitter for a variety of neuronal functions. Its loss is associated with Parkinson disease, and it is a critical agent in the mediation of pleasure and reward processes. Dopamine, due to its association with pleasurable sensations, is widely implicated in the actions of a number of drugs of abuse, including cocaine, opiates, and methamphetamines. 

A highly simplified diagram of the intestinal wall and some of the circuitry of the enteric nervous system (ENS). The ENS receives input from both the sympathetic and the parasympathetic systems and sends afferent impulses to sympathetic ganglia and to the central nervous system. Many transmitter or neuromodulator substances have been identified in the ENS see Table 6-1. ACh, acetylcholine AC, absorptive cell CM, circular muscle layer EC, enterochromaffin cell EN, excitatory neuron EPAN, extrinsic primary afferent neuron 5HT, serotonin IN, inhibitory neuron IPAN, intrinsic primary afferent neuron LM, longitudinal muscle layer MP, myenteric plexus NE, norepinephrine NP, neuropeptides SC, secretory cell SMP, submucosal plexus. 

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