Penehyclidine hydrochloride: a potential drug for treating COPD by attenuating Toll-like receptors.

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Penehyclidine hydrochloride: a potential drug for treating COPD by attenuating Toll-like receptors.

Drug Des Devel Ther. 2012;6:317-22

Authors: Xiao HT, Liao Z, Tong RS

Abstract
BACKGROUND: The aim of this review was to evaluate and summarize the available scientific information on penehyclidine hydrochloride (PHC) for the treatment of chronic obstructive pulmonary disease (COPD) as a result of its ability to attenuate Toll-like receptors. Penehyclidine hydrochloride is an anticholinergic drug manufactured in China, with both antimuscarinic and antinicotinic activity. PHC is used widely in the clinic as a reversal agent in cases of organic phosphorus poisoning and soman poisoning, but also may also have an important role as a bronchodilator in the treatment of obstructive airway disease, including asthma and, in particular, COPD.
METHODS: Our bibliographic sources included the CAPLUS, MEDLINE, REGISTRY, CASREACT, CHEMLIST, CHEMCATS, and CNKI databases, updated to September 2012. In order to assess the data in detail, we used the search terms “penehyclidine hydrochloride,” “COPD,” “muscarinic receptor,” and “toll-like receptors.” Papers were restricted to those published in the English and Chinese languages, and to “paper” and “review” as the document type. Patents were also reviewed.
RESULTS: Our survey mainly yielded the results of research on PHC and the mechanisms of COPD. COPD is a preventable and treatable disease with some significant extrapulmonary manifestations that may contribute to its severity in some patients. Recently, it has been shown that muscarinic receptors may interact with Toll-like receptors. Basic and clinical studies of the relationship between the mechanism of action and the effects of PHC in the respiratory tract have been studied by a number of laboratories and institutions. The main advantages of PHC are that it has few M(2) receptor-associated cardiovascular side effects and attenuates Toll-like receptors.
CONCLUSION: PHC may be a promising candidate agent in the treatment of COPD in the future because of its ability to attenuate Toll-like receptors. This review should be of help to those intending to research this topic further.

PMID: 23139625 [PubMed – in process]

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Therapeutic Potential of ASP3258, a Selective Phosphodiesterase 4 Inhibitor, on Chronic Eosinophilic Airway Inflammation.

Therapeutic Potential of ASP3258, a Selective Phosphodiesterase 4 Inhibitor, on Chronic Eosinophilic Airway Inflammation.

Pharmacology. 2012;90(3-4):223-32

Authors: Kobayashi M, Kubo S, Shiraki K, Iwata M, Hirano Y, Ohtsu Y, Takahashi K, Shimizu Y

Abstract
We investigated and compared the pharmacological effects of a PDE4 inhibitor ASP3258 (3-[4-(3-chlorophenyl)-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl] propanoic acid), with those of roflumilast, the most clinically advanced PDE4 inhibitor known. ASP3258 inhibited human PDE4A, 4B, 4C, and 4D with respective IC(50) values of 0.036, 0.050, 0.45, and 0.035 nmol/l, all approximately 3-6 times more potent than roflumilast. ASP3258 inhibited LPS-induced TNF-? production and PHA-induced IL-5 production in human whole blood cells with respective IC(50) values of 110 and 100 nmol/l, both approximately 10 times less potent than roflumilast. Repeatedly administered ASP3258 and roflumilast both suppressed chronic airway eosinophilia induced by repeated exposure to ovalbumin in Brown Norway rats with respective ED(50) values of 0.092 and 0.17 mg/kg. We also evaluated the toxicological profiles of ASP3258. Although PDE4 inhibitors induce emesis by mimicking the pharmacological action of an ?(2)-adrenoceptor antagonist, repeated administration of ASP3258 (3 mg/kg) had no such inhibitory effect on rats anesthetized with ?(2) – adrenoceptor agonist. PDE4 inhibitors are also known to induce vascular injury in rats. Although repeatedly administered ASP3258 (3 and 10 mg/kg) significantly increased plasma fibrinogen, a biomarker for toxicity, 1 mg/kg of ASP3258 did not. These results suggest that ASP3258 is an attractive PDE4 inhibitor for treating chronic eosinophilic airway inflammation due to asthma.

PMID: 23038661 [PubMed – in process]

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The effect of unilateral adrenalectomy on transformation of adrenal medullary chromaffin cells in vivo: a potential mechanism of asthma pathogenesis.

The effect of unilateral adrenalectomy on transformation of adrenal medullary chromaffin cells in vivo: a potential mechanism of asthma pathogenesis.

PLoS One. 2012;7(9):e44586

Authors: Hu CP, Zou YQ, Feng JT, Li XZ

Abstract
BACKGROUND: Decreased epinephrine (EPI) is an important underlying factor of bronchoconstriction in asthma. Exogenous ?(2)-adrenergic receptor agonist is one of the preferred options to treat asthma. We previously showed that this phenomenon involved adrenal medullary chromaffin cell (AMCC) transformation to a neuron phenotype. However, the underlying molecular mechanism is not fully understood. To further explore this, an asthmatic model with unilateral adrenalectomy was established in this study.
METHODOLOGY/PRINCIPAL FINDINGS: Thirty-two rats were randomly into four groups (n?=?8 each) control rats (controls), unilateral adrenalectomy rats (surgery-control, s-control), asthmatic rats (asthma), unilateral adrenalectomy asthmatic rats (surgery-induced asthma, s-asthma). Asthmatic rats and s-asthmatic rats were sensitized and challenged with ovalbumin (OVA). The pathological changes in adrenal medulla tissues were observed under microscopy. EPI and its rate-limiting enzyme, phenylethanolamine N-methyl transferase (PNMT), were measured. Peripherin, a type III intermediate filament protein, was also detected in each group. The asthmatic rats presented with decreased chromaffin granules and swollen mitochondria in AMCCs, and the s-asthmatic rats presented more serious pathological changes than those in asthmatic rats and s-control rats. The expressions of EPI and PNMT in asthmatic rats were significantly decreased, as compared with levels in controls (P<0.05), and a further decline was observed in s-asthmatic rats (P<0.05). The expression of peripherin was higher in the asthmatic rats than in the controls, and the highest level was found in the s-asthmatic rats (P<0.05).
CONCLUSION/SIGNIFICANCE: Compared with asthmatic rats and s-control rats, the transformation tendency of AMCCs to neurons is more obvious in the s-asthmatic rats. Moreover, this phenotype alteration in the asthmatic rats is accompanied by reduced EPI and PNMT, and increased peripherin expression. This result provides further evidence to support the notion that phenotype alteration of AMCCs contributes to asthma pathogenesis.

PMID: 22957086 [PubMed – in process]

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“cinnamon challenge” has potential to be deadly – CBS News


CBS News

"cinnamon challenge" has potential to be deadly
CBS News
Although only 25 percent of those calling needed hospital attention, the challenge can be especially dangerous for those with breathing problems like asthma or chronic obstructive pulmonary disease (COPD). Glatter says the reason why most people can't
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Potential benefits from vitamin D supplementation for children with asthma – HealthCanal.com

Potential benefits from vitamin D supplementation for children with asthma
HealthCanal.com
Several recent studies have suggested that low serum vitamin D can influence the severity of asthma and/or atopy. However age specific relationships of vitamin D were not addressed. In a manuscript in The Journal of Allergy & Clinical Immunology (JACI)

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MediciNova and University of Colorado Boulder Collaborate on Potential Novel … – MarketWatch (press release)

MediciNova and University of Colorado Boulder Collaborate on Potential Novel
MarketWatch (press release)
Ibudilast has been used in asthma and post-stroke disorders in Japan for around 20 years. MediciNova has demonstrated utility of ibudilast in neurological disorders at higher doses with encouraging outcomes in company-sponsored clinical trials in

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Discovery Of Two Genetic Variants Indicates Potential Of New Asthma Treatment – Medical News Today

Discovery Of Two Genetic Variants Indicates Potential Of New Asthma Treatment
Medical News Today
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Researchers find potential new treatment for asthma sufferers – The Cherokeean Herald

Researchers find potential new treatment for asthma sufferers
The Cherokeean Herald
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