Histamine central nervous system

Carcinine P-alanyl-histamine Central nervous system and heart 1975... 

Histamine is a biogenic amine that is widely distributed in the body and functions as a major mediator of inflammation and allergic reactions, as a physiological regulator of gastric acid secretion in the stomach, as a neurotransmitter in the central nervous system (CNS) and may also have a role in tissue growth and repair. 

There are a number of side-effects of opiates that are due to their actions on opiate receptors outside the central nervous system. Opiates constrict the pupils by acting on the oculomotor nucleus and cause constipation by activating a maintained contraction of the smooth muscle of the gut which reduces motility. This diminished propulsion coupled with opiates reducing secretion in the gut underlie the anti-diarrhoeal effect. Opiates contract sphincters throughout the gastrointestinal tract. Although these effects are predominantly peripheral in origin there are central contributions as well. Morphine can also release histamine from mast cells and this can produce irritation and broncho-spasm in extreme cases. Opiates have minimal cardiovascular effects at therapeutic doses. 

Histamine produces its pharmacological actions by three subtypes of receptors the postsynaptic Hi and H2 receptors and the presynaptic H3 receptor. The H3 receptor is mainly located in the central nervous system (CNS), where it acts as an inhibitory autoreceptor in the central histaminergic neuronal pathways [176]. A number of therapeutic applications have been proposed for selective H3 receptor antagonists, including several CNS disorders such as Alzheimer s disease. Attention Deficit Hyperactivity Disorder, Schizophrenia, or for enhancing memory or obesity control. 

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. 

American Academy of Pediatrics allergen immunotherapy allergic rhinitis central nervous system histamine-1 receptor antagonist immunoglobulin E over the counter perennial allergic rhinitis seasonal allergic rhinitis... 

Timmerman, H. (1989). Histamine receptors in the central nervous system. Pharm. Weekbl. Sci. 20(11), 146-50. 

Currently, three subtypes of histamine receptors are proposed and H2 receptors are found in peripheral tissues and the central nervous system (CNS), and receptors are found in the CNS. The second messenger pathway that mediates Hrreceptor stimulation is... 

Although histamine is not stored in neurons outside of the central nervous system, mast-cell-derived histamine can modify peripheral sensory nerve function. Both acute and chronic pain states can result from inflammation or peripheral nerve cell injury, and there is substantial evidence that mast cell histamine participates in these disorders. 

Nishibori, M., Tahara, A, Sawada, K., Sakiyama, J., Nakaya, N. and Saeki, K. Neuronal and vascular localization of histamine N-methyltransferase in the bovine central nervous system. Eur. J. Neurosci. 12 415-424,2000. 

Histamine Hj receptor Antagonist Acute (central nervous system) Sedation Diphenhydramine27... 

Binds to DNA and prevents separation of the helical strands Affects neuronal transmissions Binds to opiate receptors and blocks pain pathway Acts as central nervous system depressant Inhibits Na/K/ATPase, increases intracellular calcium, and increases ventricular contractibility Blocks the actions of histamine on Hi receptor Blocks ai-adrenergic receptor, resulting in decreased blood pressure Inhibits reuptake of 5-hydroxytryptamine (serotonin) into central nervous system neurons Inhibits cyclooxygenase, inhibition of inflammatory mediators Inhibits replication of viruses or tumor cells Inhibits HIV reverse transcriptase and DNA polymerase Antagonizes histamine effects... 

Histamine (2-[4-imidazole] ethylamine) is a low-molecular-weight amine synthesized from L-histidine exclusively by histidine decarboxylase. It is produced by various cells throughout the body, including central nervous system neurons, gastric mucosa parietal cells, mast cells, basophils and lymphocytes [1-4]. Since its discovery as a uterine... 

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. 

Witkin JM, Nelson DL. Selective histamine H3 receptor antagonists for treatment of cognitive deficiencies and other disorders of the central nervous system. Pharmacol Ther 2004 103 1-20. 

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. 

In the mucosa of the gastrointestinal tract histamine is present in enterochromaffin cells. These cells are thought to contain the histamine which is involved in the stimulation of gastric acid secretion. In the central nervous system there are histaminergic neurons. 

Sinus problems, hay fever, bronchial asthma, hives, eczema, contact dermatitis, food allergies, and reactions to drugs are all allergic reactions associated with the release of histamine and other autocoids, such as serotonin, leukotrienes, and prostaglandins. Histamine release is frequently associated with various inflammatory states and may be increased in urticarial reactions, mastocytosis, and basophilia. Histamine also acts as a neurotransmitter in the central nervous system (CNS). Upon release from its storage sites, histamine exerts effects ranging from mild irritation and itching to anaphylactic shock and eventual death. 

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). 

The bronchodilation produced by the methylxanthines is the major therapeutic action in asthma. Tolerance does not develop, but adverse effects, especially in the central nervous system, may limit the dose (see below). In addition to their effect on airway smooth muscle, these agents—in sufficient concentration—inhibit antigen-induced release of histamine from lung tissue their effect on mucociliary transport is unknown. 

The first phenothiazine antipsychotic drugs, with chlorpromazine as the prototype, proved to have a wide variety of central nervous system, autonomic, and endocrine effects. Although efficacy of these drugs is primarily driven by D2-receptor blockade, their adverse actions were traced to blocking effects at a wide range of receptors including a adrenoceptors and muscarinic, Hi histaminic, and 5-HT2 receptors. 

The term "H3 receptor" has been coined by Arrang et al.1 H3 receptors are located on paracrine cells and on neurones activation of H3 receptors usually causes inhibition of the release of the respective mediator or neurotransmitter. The receptor characterized by Arrang et al.1 is an example of an autoreceptor, i.e. of a receptor via which the transmitter released from a given neurone influences its own release. H3 receptor-mediated inhibition of the release of transmitters other than histamine has also been described such receptors are known as heteroreceptors. The present review will focus on H3 heteroreceptors in the central nervous system (CNS) in separate chapters of this book, H3 autoreceptors, H3 heteroreceptors in the neuroendocrine system as well as H3 receptor-mediated modulation of transmitter release in vivo will be considered. A separate article will also deal with H3 heteroreceptors in peripheral tissues although an example of an H3 receptor in the retina will be covered in our chapter, due to the close relationship between CNS and retina2. 

Radiolabelled compounds for the histamine H3 receptor have been proven to be of great value in pharmacological and biochemical research. Some iodinated and tritiated compounds haven become standard research tools. In contrast, the development of PET or SPECT ligands has been proven to be troublesome. So far there has been no radiolabelled compound which is taken up into the brain in reasonable amounts to allow for PET or SPECT studies of the H3 receptor in the brain. The search for new radiolabelled compounds is still going on however, as is research to find out why these radiolabelled compounds do not enter the brain as opposed to their non-radiolabelled equivalents. One can detect pharmacological effects which can only be caused by central nervous system activity of these non-radiolabelled compounds. In view of the... 

Initially, the histamine H3 receptor was characterized as an inhibitory presynaptic autoreceptor in the central nervous system (CNS) [1,2], but more recently it has been found to occur also on non-histaminergic axon terminals modulating the release of several other important neurotransmitters [3,4],... 

The tertiary members of these classes (Figure 8-2) are often used for their effects on the eye or the central nervous system. Many antihistaminic (see Chapter 16 Histamine, Serotonin, the Ergot Alkaloids), antipsychotic (see Chapter 29 Antipsychotic Agents Lithium), and antidepressant (see Chapter 30 Antidepressant Agents) drugs have similar structures and, predictably, significant antimuscarinic effects. 

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