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      Pleiotropic effects and pharmacological properties of penehyclidine hydrochloride

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          Abstract

          Background

          Penehyclidine hydrochloride (PHC) is an anticholinergic drug manufactured in China. It is used widely in clinics as a reversal agent in cases of organic phosphorus poisoning and as a preanesthetic medication. Compared with other anticholinergic agents, PHC confers substantial advantages. Here, in this review, we focus on its important clinical effects for organic phosphorus poisoning, preanesthetic medication, and the protective effects on certain visceral organs.

          Materials and methods

          Our bibliographic sources include the PubMed and China National Knowledge Infrastructure (CNKI) databases, updated in March 2018. To assess the data in detail, we used the search terms “penehyclidine hydrochloride,” “preanesthetic medication,” and “organic phosphorus.” Papers were restricted to those published in the English and Chinese languages, and to “paper” and “review” as the document type.

          Results

          PHC can effectively antagonize the symptoms of central and peripheral poisoning caused by organophosphorus poisoning. As a preanesthetic medication, it can not only effectively reduce mucus secretion and vascular infiltration but can also relax airway smooth muscles, dilate bronchioles in pulmonary conditions such as bronchiectasis, and increase pulmonary dynamic compliance. It can also prevent reflexive actions of the vagus nerve caused by excessive acetylcholine release such as abnormal airway contraction. Furthermore, it can strengthen sedation, bidirectionally regulate heart rate, and effectively inhibit respiratory secretions. In recent studies, PHC was shown to also have protective effects on various organs, such as the heart, lungs, brain, kidneys, intestines, and liver.

          Conclusion

          PHC has beneficial pharmacological properties used in the treatment of organophosphorus poisoning and as a preanesthetic medication for its few side effects. It also has protective effects on multiple organs, suggesting that PHC has extensive clinical application value which is worth further research. This review should be of help to those intending to research these topics further.

          Most cited references43

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          Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans.

          Animal life is controlled by neurons and in this setting cholinergic neurons play an important role. Cholinergic neurons release ACh, which via nicotinic and muscarinic receptors (n- and mAChRs) mediate chemical neurotransmission, a highly integrative process. Thus, the organism responds to external and internal stimuli to maintain and optimize survival and mood. Blockade of cholinergic neurotransmission is followed by immediate death. However, cholinergic communication has been established from the beginning of life in primitive organisms such as bacteria, algae, protozoa, sponge and primitive plants and fungi, irrespective of neurons. Tubocurarine- and atropine-sensitive effects are observed in plants indicating functional significance. All components of the cholinergic system (ChAT, ACh, n- and mAChRs, high-affinity choline uptake, esterase) have been demonstrated in mammalian non-neuronal cells, including those of humans. Embryonic stem cells (mice), epithelial, endothelial and immune cells synthesize ACh, which via differently expressed patterns of n- and mAChRs modulates cell activities to respond to internal or external stimuli. This helps to maintain and optimize cell function, such as proliferation, differentiation, formation of a physical barrier, migration, and ion and water movements. Blockade of n- and mACHRs on non-innervated cells causes cellular dysfunction and/or cell death. Thus, cholinergic signalling in non-neuronal cells is comparable to cholinergic neurotransmission. Dysfunction of the non-neuronal cholinergic system is involved in the pathogenesis of diseases. Alterations have been detected in inflammatory processes and a pathobiologic role of non-neuronal ACh in different diseases is discussed. The present article reviews recent findings about the non-neuronal cholinergic system in humans.
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            Patterns and problems of deliberate self-poisoning in the developing world.

            Deliberate self-harm is a major problem in the developing world, responsible for around 600 000 deaths in 1990. The toxicity of available poisons and paucity of medical services ensure that mortality from self-poisoning is far greater in the tropics than in the industrialized world. Few data are available on the poisons most commonly used for self-harm in different parts of the world. This paper reviews the literature on poisoning, to identify the important poisons used for self-harm in these regions. Pesticides are the most important poison throughout the tropics, being both common and associated with a high mortality rate. In some regions, particular pesticides have become the most popular method of self-harm, gaining a notoriety amongst both health-care workers and public. Self-poisoning with medicines such as benzodiazepines and antidepressants is common in urban areas, but associated with few deaths. The antimalarial chloroquine appears the most significant medicine, self-poisoning being common in both Africa and the Pacific region, and often fatal. Paracetamol (acetaminophen) is used in many countries but in few has it reached the popularity typical of the UK. Domestic and industrial chemicals are responsible for significant numbers of deaths and long-term disabilities world-wide. Self-poisoning with plant parts, although uncommon globally, is locally popular in some regions. Few of these poisons have specific antidotes. This emphasizes the importance of determining whether interventions aimed at reducing poison absorption actually produce a clinical benefit, reducing death and complication rates. Future research to improve medical management and find effective ways of reducing the incidence of self-harm, together with more widespread provision of interventions proven to be effective, could rapidly reduce the number of deaths from self-poisoning in the developing world.
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              Cholinergic Modulation of the Immune System Presents New Approaches for Treating Inflammation.

              The nervous system and immune system have broad and overlapping distributions in the body, and interactions of these ubiquitous systems are central to the field of neuroimmunology. Over the past two decades, there has been explosive growth in our understanding of neuroanatomical, cellular, and molecular mechanisms that mediate central modulation of immune functions through the autonomic nervous system. A major catalyst for growth in this field was the discovery that vagal nerve stimulation (VNS) caused a prominent attenuation of the systemic inflammatory response evoked by endotoxin in experimental animals. This effect was mediated by acetylcholine (ACh) stimulation of nicotinic receptors on splenic macrophages. Hence, the circuit was dubbed the "cholinergic anti-inflammatory pathway". Subsequent work identified the α7 nicotinic ACh receptor (α7nAChR) as the crucial target for attenuation of pro-inflammatory cytokine release from macrophages and dendritic cells. Further investigation made the important discovery that cholinergic T cells within the spleen and not cholinergic nerve cells were the source of ACh that stimulated α7 receptors on splenic macrophages. Given the important role that inflammation plays in numerous disease processes, cholinergic anti-inflammatory mechanisms are under intensive investigation from a basic science perspective and in translational studies of animal models of diseases such as inflammatory bowel disease and rheumatoid arthritis. This basic work has already fostered several clinical trials examining the efficacy of VNS and cholinergic therapeutics in human inflammatory diseases. This review provides an overview of basic and translational aspects of the cholinergic anti-inflammatory response and relevant pharmacology of drugs acting at the α7nAChR.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2018
                05 October 2018
                : 12
                : 3289-3299
                Affiliations
                Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, People’s Republic of China, 18710168703@ 123456163.com
                Author notes
                Correspondence: Jun Ma, Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, 2 Anzhen Road, Chaoyang, Beijing 100029, People’s Republic of China, Tel +86 133 7010 3571, Email 18710168703@ 123456163.com
                Article
                dddt-12-3289
                10.2147/DDDT.S177435
                6181090
                30323561
                6d53b782-c1bb-430f-be48-d155d72b217b
                © 2018 Wang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                penehyclidine hydrochloride,preanesthetic medication,organic phosphorus,organ protection,ischemia-reperfusion,septic shock,central sedation

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