Neurotransmitter receptors histamine receptor

In 1966, the name was proposed (5) for receptors blocked by the at that time known antihistamines. It was also speculated that the other actions of histamine were likely to be mediated by other histamine receptors. The existence of the H2 receptor was accepted in 1972 (6) and the receptor was recognized in rat brain in 1983 (7). receptors in the brain appear to be involved in the feedback control of both histamine synthesis and release, whereas release of various other neurotransmitters, eg, serotinin (5-HT), dopamine, noradrenaline, and acetylcholine, is also modulated (8) (see Neuroregulators). 

Numerous neurotransmitter receptors are located in the vomiting center, CTZ, and GI tract. Examples of such receptors include cholinergic and histaminic, dopaminergic, opiate, serotonin, neurokinin (NK), and benzodiazepine receptors. Theoretically, chemotherapeutic agents, their metabolites, or other emetic compounds trigger the process of emesis through stimulation of one or more of these receptors. 

The S-enantiomer of citalopram (escitalopram) is over 100 times more potent in inhibiting the reuptake of 5-HT into brain slices than the R-form and is devoid of any activity at the neurotransmitter of other receptor types (racemic citalopram has an affinity for histamine receptors and causes sedation). In in vivo studies, escitalopram is more potent than the R-form or the racemate in releasing 5-HT in the cortex of conscious rats it has been... 

Examples maprotiline a bridged" tricyclic with affinity for histamine, HI, and alpha-1 adrenoceptors. Causes seizures reboxetine not cardiotoxic does not have an affinity for any neurotransmitter receptors... 

Histamine, an important mediator (local signaling substance) and neurotransmitter, is mainly stored in tissue mast cells and basophilic granulocytes in the blood. It is involved in inflammatory and allergic reactions. Histamine liberators such as tissue hormones, type E immunoglobulins (see p. 300), and drugs can release it. Histamine acts via various types of receptor. Binding to Hi receptors promotes contraction of smooth muscle in the bronchia, and dilates the capillary vessels and increases their permeability. Via H2 receptors, histamine slows down the heart rate and promotes the formation of HCl in the gastric mucosa. In the brain, histamine acts as a neurotransmitter. 

The role of histamine as a central neurotransmitter has long been recognized, and a considerable amount of research has been directed toward elucidating its central effects and receptors. The additional discovery of the duality of the histamine receptor (i.e., both inside and outside the brain) has added another dimension to this complex field, leading to new and successful therapeutic as well as theoretical investigations. 

NEUROTRANSMITTERS AND THEIR RECEPTORS 4.6.1 Structure, Conformation, and Equilibria of Histamine... 

Hj, Hj, and Hj receptors are present in the CNS. Tricyclic antidepressant drugs seem to interact with histamine receptors in the CNS. Histamine receptor subtypes in the CNS and the central neurotransmitter role of histamine have been the subject of many recent investigations. Currently there are three central histamine receptors ... 

The most popular OTC sleep aids are those that contain antihistamines such as diphenhydramine or doxylamine (Table 3.1). As noted in Chapter 1, nerve cells in the brain communicate with each other by secreting chemicals called neurotransmitters. One such neurotransmitter that regulates sleep is histamine. When histamine is released by a nerve cell, it diffuses over to the target nerve cell and binds to specialized proteins called receptors located on the outer surface of the nerve cell. These receptors are specially designed to bind only histamine, and when they do, the target nerve cell will become either activated or deactivated. In the brain, histamine serves the function of keeping us awake, and when drugs such as antihistamines are taken, they block the ability of histamine receptors to bind histamine. 

Still other pharmacologic actions are associated with the conventional antipsychotic drugs. These include generally undesired activity at alpha 1 adrenergic receptors as well as at histamine 1 receptors, as already discussed (Fig. 11—7). Thus, conventional antipsychotic drugs have activities at three of the same neurotransmitter receptors... 

FIGURE 18.4 Pharmacologist s view of emetic stimuli. Myriad signaling pathways lead from the periphery to the emetic center. Stimulants of these pathways are noted in italics. These pathways involve specific neurotransmitters and their receptors (bold text). Receptors are shown for dopamine, D acetylcholine (muscarinic), M histamine, H and 5-hydroxytryptamine, 5-HT. Some of these receptor types also may mediate signaling in the emetic center. This knowledge offers a rationale for current antiemetic therapy. 

Apart from its role as a major mediator of inflammation and allergic reactions and as physiological regulator of gastric acid secretion, histamine is also a neurotransmitter in the CNS. Central histaminergic cell bodies are located in the posterior hypothalamus and project diffusely to almost all brain regions and to the spinal cord. There are four types of histamine receptors, all G-protein-coupled, Hi, H2, H3 and H4. Hi receptors couple to Gq/11 proteins. H2 receptors couple to Gs. H3 and H4 receptors couple to Gi/o. 

If presynaptic histamine receptors are more uniform than presynaptic dopamine receptors, the contrary holds true for presynaptic serotonin receptors they are even more diverse than presynaptic dopamine receptors. As mentioned in the Introduction, presynaptic 5-HT3 receptors, being ligand-gated ion channels, are covered in the chapter by Dorostkar and Boehm and will be mentioned here only occasionally. Presynaptic G protein-coupled 5-HT receptors inhibit the release of serotonin from serotonergic axon terminals and inhibit or enhance the release of other neurotransmitters (Table 4). 

In addition to their affinity for dopamine receptors, which appears to be essential for their therapeutic activity, all neuroleptics in current clinical use have affinities for other types of neurotransmitter receptor. Mention has already been made of the side effects of the weaker neuroleptics such as chlorpromazine for histamine-1, muscarinic and alpha-1 adrenoceptors. However, it is now apparent that many of the newer, atypical, neuroleptics have an affinity for subtypes of 5-HT (particularly 5-HT2A) receptors which may be beneficial in reducing the frequency of extrapyramidal side effects. Thus neuroleptics may now be broadly classified into those which are selective antagonists of D2 receptors, those that are D2 and D3 receptor antagonists, those blocking both D and D2 receptors and, a most important group of novel neuroleptics, those that are antagonists of 5-HT2 and D2 receptors. 

Q4 Antihistamines are effective in managing many of the troublesome symptoms of allergic rhinitis. Histamine is a neurotransmitter and a mediator of type 1 hypersensitivity reactions, such as urticaria and hay fever. There are several types of histamine receptors and these allergic conditions can be treated with Hi receptor antagonists, such as promethazine, chlorphenamine and fexofenadine. First-generation antihistamines, such as promethazine, cause sedation and possess side effects associated with actions on muscarinic receptors. Fexofenadine is a newer drug with a longer duration of action, which does not sedate the patient. 

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