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      Brain Histamine N-Methyltransferase As a Possible Target of Treatment for Methamphetamine Overdose

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          Abstract

          Stereotypical behaviors induced by methamphetamine (METH) overdose are one of the overt symptoms of METH abuse, which can be easily assessed in animal models. Currently, there is no successful treatment for METH overdose. There is increasing evidence that elevated levels of brain histamine can attenuate METH-induced behavioral abnormalities, which might therefore constitute a novel therapeutic treatment for METH abuse and METH overdose. In mammals, histamine N-methyltransferase (HMT) is the sole enzyme responsible for degrading histamine in the brain. Metoprine, one of the most potent HMT inhibitors, can cross the blood–brain barrier and increase brain histamine levels by inhibiting HMT. Consequently, this compound can be a candidate for a prototype of drugs for the treatment of METH overdose.

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          Most cited references108

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          A review of the clinical pharmacology of methamphetamine.

          To examine the literature regarding clinical pharmacokinetics, direct effects and adverse clinical outcomes associated with methamphetamine use. Relevant literature was identified through a PubMed search. Additional literature was obtained from relevant books and monographs. The mean elimination half-life for methamphetamine is approximately 10 hours, with considerable inter-individual variability in pharmacokinetics. Direct effects at low-to-moderate methamphetamine doses (5-30 mg) include arousal, positive mood, cardiac stimulation and acute improvement in cognitive domains such as attention and psychomotor coordination. At higher doses used typically by illicit users (> or =50 mg), methamphetamine can produce psychosis. Its hypertensive effect can produce a number of acute and chronic cardiovascular complications. Repeated use may induce neurotoxicity, associated with prolonged psychiatric symptoms, cognitive impairment and an increased risk of developing Parkinson's disease. Abrupt cessation of repeated methamphetamine use leads to a withdrawal syndrome consisting of depressed mood, anxiety and sleep disturbance. Acute withdrawal lasts typically for 7-10 days, and residual symptoms associated with neurotoxicity may persist for several months.
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            The role of mast cells in allergic inflammation.

            Kawa Amin (2012)
            The histochemical characteristics of human basophils and tissue mast cells were described over a century ago by Paul Ehrlich. When mast cells are activated by an allergen that binds to serum IgE attached to their FcɛRI receptors, they release cytokines, eicosanoids and their secretory granules. Mast cells are now thought to exert critical proinflammatory functions, as well as potential immunoregulatory roles, in various immune disorders through the release of mediators such as histamine, leukotrienes, cytokines chemokines, and neutral proteases (chymase and tryptase). The aim of this review is to describe the role of mast cells in allergic inflammation. Mast cells interact directly with bacteria and appear to play a vital role in host defense against pathogens. Drugs, such as glucocorticoids, cyclosporine and cromolyn have been shown to have inhibitory effects on mast cell degranulation and mediator release. This review shows that mast cells play an active role in such diverse diseases as asthma, rhinitis, middle ear infection, and pulmonary fibrosis. In conclusion, mast cells may not only contribute to the chronic airway inflammatory response, remodeling and symptomatology, but they may also have a central role in the initiation of the allergic immune response, that is providing signals inducing IgE synthesis by B-lymphocytes and inducing Th2 lymphocyte differentiation. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              How addictive drugs disrupt presynaptic dopamine neurotransmission.

              The fundamental principle that unites addictive drugs appears to be that each enhances synaptic dopamine by means that dissociate it from normal behavioral control, so that they act to reinforce their own acquisition. This occurs via the modulation of synaptic mechanisms that can be involved in learning, including enhanced excitation or disinhibition of dopamine neuron activity, blockade of dopamine reuptake, and altering the state of the presynaptic terminal to enhance evoked over basal transmission. Amphetamines offer an exception to such modulation in that they combine multiple effects to produce nonexocytic stimulation-independent release of neurotransmitter via reverse transport independent from normal presynaptic function. Questions about the molecular actions of addictive drugs, prominently including the actions of alcohol and solvents, remain unresolved, but their ability to co-opt normal presynaptic functions helps to explain why treatment for addiction has been challenging. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Drug Target Insights
                Drug Target Insights
                Drug Target Insights
                Drug Target Insights
                Libertas Academica
                1177-3928
                2016
                02 March 2016
                : 10
                : 1-7
                Affiliations
                [1 ]Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
                [2 ]Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
                [3 ]New Mexico VA Healthcare System/BRINM, Albuquerque, NM, USA.
                Author notes
                Article
                dti-10-2016-001
                10.4137/DTI.S38342
                4777238
                26966348
                da5feebe-8e95-4d15-acf2-9f32294e8ace
                © 2016 the author(s), publisher and licensee Libertas Academica Ltd.

                This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.

                History
                : 23 December 2015
                : 25 January 2016
                : 27 January 2016
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                methamphetamine,overdose,stereotyped behavior,histamine n-methyltransferase,brain histaminergic system,metoprine

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