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

Abstract

BackgroundThe 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.MethodsOur 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.ResultsOur 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 M2 receptor-associated cardiovascular side effects and attenuates Toll-like receptors.ConclusionPHC 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.

Mechanism of penehyclidine hydrochloride on a dysmenorrhea rat model

“…TLR 3 is involved in the recognition of mRNA, dsRNA, and viruses, while TLR 4 is a key component of the initial injury response via reacting toward bacterial endotoxin and multiple endogenous ligands. Related studies have shown that PHC could relax the smooth muscle tissue of COPD by attenuating TLRs (Xiao et al, ). Therefore, we speculate that PHC may also relax the smooth muscle of the uterus in primary dysmenorrhea via regulating TLRs.…”

“…Hirata et al demonstrated that estradiol treatment suppressed the expression of TLR 4 mRNA in human endometrial stromal cells (Hirata et al, ); therefore, the low expression of TLR 4 in the model group may be attributed to the administration of estradiol. Furthermore, related studies reported that PHC could relax the smooth muscle of COPD by attenuating TLRs (Xiao et al, ). Therefore, we speculated that PHC may also regulate TLRs in the uterine tissue, and, the expression of TLR 4 was decreased in the PHC group versus the model group.…”

“…PHC is widely used in the clinical context as an antagonist of organic phosphorus poisoning and soman (Li et al, ; Wang et al, ). So far, PHC has obtained worldwide popularity as an anesthetic premedication and as treatment for smooth muscle spasm (Wang, Ren, & Zhu, ; Xiao, Liao, & Tong, ). Therefore, this study assumed that PHC may relax the contractions of the uterus.…”

“…Primary dysmenorrhea is associated with inflammation, and it has been shown to produce several cytokines, chemokines, growth factors, and other mediators and recruits leukocytes to the area of injury or infection (Kracht & Saklatvala, ; Moss & Blaser, ; White, Bhangoo, & Miller, ). Related studies have shown that PHC could relax smooth muscles in chronic obstructive pulmonary disease (COPD) by attenuating TLRs (Xiao et al, ). Therefore, this study hypothesized that PHC may also relax the smooth muscle of the uterus in primary dysmenorrhea via regulating TLRs.…”

Development and validation of an improved HPLC-MS/MS method for comparative pharmacokinetics of penehyclidine hydrochloride following a single intravenous or intramuscular injection

“…1) is an anticholinergic drug with both antimuscarinic and antinicotinic activity [1,2]. Currently, PHC is widely used in clinical practice as a reversal agent in cases of organophosphorus and soman poisoning [3], and it is also widely used as a preoperative anticholinergic owing to its strong selective antagonistic action for M 1 /M 3 /N 1 /N 2 receptors and fewer M 2 receptor-associated cardiovascular side effects compared with other anticholinergics, such as atropine [2].…”