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

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.

Keywords: Toll-like receptors; chronic obstructive pulmonary disease; penehyclidine hydrochloride.

Figure 1

Toll-like receptor 4 signal pathway. Abbreviations: TLR-4, toll-like receptor 4; MyD88, myeloid differentiation factor 88; TRIF, TIR-domain-containing adapter-inducing interferon-β; Mal, MyD88-adapter-like; TRAM, TRIF-related adaptor molecule; TRAF, TNF-receptor-associated factor; PI3K, phosphoinositide 3-kinase; TKs, protein tyrosine kinases; PyK2, protein tyrosine kinase 2; SyK, spleen tyrosine kinase; IRAK, IL-1R-associated kinases; MAPKs, mitogen-activation protein kinases; IKK, IkappaB kinase; PKB, protein kinase B; NEMO, NF-κB essential modulator; NF-κB, nuclear transcription factor kappa-B; TGF, transforming growth factor; MKK, mitogen-activated protein kinase kinase; IRF, IFN regulatory factor; RANTES, Regulated on activation normal T expressed and secreted; TNF, Tumor necrosis factor; IL, interleukin; INF, interferon; IP-10, interferon-gamma inducible protein 10.