Abstract:
:Derivatization of phenothiazine (PTZ, 1) has been a commonly used method to develop drugs with various pharmacological properties. In the present study, a series of PTZ derivatives 1-11 were investigated on the inhibition of the cloned α7 subunit of the human nicotinic acetylcholine receptor (α7-nAChR) expressed in Xenopus oocytes by using the two-electrode voltage-clamp technique. In the first series of experiments, the effect of unsubstituted phenothiazine 1 on α7-nAChRs was compared with that of the N3,N7-diaminophenothiazin-5-ium derivative 2, and of sequentially methylated derivatives 3-6. In the second set of experiments, the effects of N3,N7-tetra-ethyl- to n-hexylphenothiazin-5-ium derivatives 7-11 were tested. Despite the lack of activity found for 1, a reversible inhibition of α7-nAChRs, ranging from moderate to potent, was observed as a result of a sequential amine- and methylamine substitution of 1. The inhibition of ACh (100 μM)-induced currents was concentration-dependent with IC(50) values ranging from 0.4 to 16.8 μM. However, an optimal inhibitory activity was achieved by prolongation of alkyl chains up to propyl size, as found in PTZ derivative 8, whereas further lengthening of alkyl chains to n-butyl-, n-pentyl-, or n-hexyl groups resulted in inactive derivatives 9-11. The results evidently suggest the presence of a lipophilic binding pocket of narrow tolerability on the receptor protein. These results emphasize the importance of amine and/or alkylamine moieties for the inhibitory effect of PTZ derivatives and provide further insights for the development of novel antagonists targeting α7-nAChRs.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Sadek B,Ashoor A,Al Mansouri A,Lorke DE,Nurulain SM,Petroianu G,Wainwright M,Oz Mdoi
10.1016/j.phrs.2012.05.008subject
Has Abstractpub_date
2012-09-01 00:00:00pages
213-8issue
3eissn
1043-6618issn
1096-1186pii
S1043-6618(12)00116-8journal_volume
66pub_type
杂志文章abstract::Reproductive dysfunction in the female diabetic rat is associated with impaired hypothalamic-hypophyseal system, anovulation, insufficiency of ovarian steroidogenesis and spontaneous failure of pregnancy. Formation of decidua, the highly modified endometrium of pregnancy and pseudopregnancy could only be achieved when...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2000.0673
更新日期:2000-08-01 00:00:00
abstract::The potential drug-to-drug interaction between darunavir and raltegravir in the setting of HIV infection is a highly debated issue still unresolved. In the present study we have evaluated the pharmacokinetics of darunavir and ritonavir in 53 HIV-1 infected patients with or without concomitant raltegravir administratio...
journal_title:Pharmacological research
pub_type: 临床试验,杂志文章
doi:10.1016/j.phrs.2011.09.006
更新日期:2012-02-01 00:00:00
abstract::This paper describes a new sensitive gas chromatographic method with electron capture detector to assay estazolam in human plasma, which has been developed and validated for pharmacokinetic purposes. The drug and the internal standard (triazolam) were extracted from plasma buffered at pH 9.0 into toluene and analysed ...
journal_title:Pharmacological research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1006/phrs.1997.0144
更新日期:1997-04-01 00:00:00
abstract::The vascular endothelial growth factor receptor-1 (VEGFR-1) is a membrane receptor for VEGF-A, placenta growth factor (PlGF) and VEGF-B that plays a crucial role in melanoma invasiveness, vasculogenic mimicry and tumor-associated angiogenesis. Furthermore, activation of VEGFR-1 is involved in the mobilization of myelo...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.104957
更新日期:2020-09-01 00:00:00
abstract::The most frequent cause of mortality and morbidity in industrialized countries is coronary artery disease (CAD), which in Europe alone is responsible for around two million deaths per year. In 2001 it accounted for about 260,000 hospital discharges in Italy. The costs of CAD treatment in Italy--which were borne by the...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2006.04.002
更新日期:2006-08-01 00:00:00
abstract::Pulmonary fibrosis is a chronic condition characterized by progressive scarring of lung parenchyma. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (PEA-um(®)), an endogenous fatty acid amide, in mice subjected to idiopathic pulmonary fibrosis. Idiopathic pul...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.07.010
更新日期:2016-09-01 00:00:00
abstract::As one classic anticancer drug, clinical application of Doxorubicin (Dox) is limited due to its side effects. In our previous work, we have investigated the drug targets to treat Dox-induced cardiotoxicity, hepatotoxicity and nephrotoxicity. In this paper, the mechanisms and new drug-target associated with Dox-induced...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2019.104276
更新日期:2019-08-01 00:00:00
abstract::The mechanism for the pathological increase in cell death in various disease states e.g. HIV immunodefficiency or even ageing or Alzheimer's disease, occurs by complex and as yet undefined mechanism(s) related to immunological, virological or biochemical disturbances (i.e. energy depletion, oxidative stress, increased...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043-6618(05)80044-1
更新日期:1995-12-01 00:00:00
abstract::Treatment of MC3T3E-1 osteoblast cultures with combined interferon- gamma(IFN- gamma), lipopolysaccharide (LPS) and tumor necrosis factor- alpha(TNF- alpha) induces expressions of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6), resulting in sustained releases of large amounts of nitric oxide and IL-6....
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2000.0778
更新日期:2001-03-01 00:00:00
abstract::The molecular complexity of human breast cancer (BC) renders the clinical management of the disease challenging. Long non-coding RNAs (lncRNAs) are promising biomarkers for BC patient stratification, early detection, and disease monitoring. Here, we identified the involvement of the long intergenic non-coding RNA 0108...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.105249
更新日期:2020-11-01 00:00:00
abstract::Anti-hypertensive agents may differently stimulate compensatory neuro-hormonal mechanisms and induce different effects on the cardiovascular remodeling and function. The combination of low doses of the two synergistic drugs may lead to a lesser activation of counter regulatory mechanisms and could provide optimal ther...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2004.10.010
更新日期:2005-04-01 00:00:00
abstract::There is considerable evidence to support the role of anandamide (AEA), an endogenous ligand of cannabinoid receptors, in neuropathic pain modulation. AEA also produces effects mediated by other biological targets, of which the transient receptor potential vanilloid type 1 (TRPV1) has been the most investigated. Both,...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.06.012
更新日期:2016-09-01 00:00:00
abstract::The concept of compartment evolved in the contexts of radioactivity, physiology, pharmacology and tracer kinetics. Recently compartmental models have been compared with 'physiological models', even though in most cases the same, or stricter hypotheses, are necessary for the validity of these latter models. This paper ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.2001.0873
更新日期:2001-10-01 00:00:00
abstract::Epidemiological, clinical and animal studies revealed that sex differences exist in the manifestation and outcome of cardiovascular disease (CVD). The underlying molecular mechanisms implicated in these sex differences are not fully understood. The reasons for sex differences in CVD are definitely multifactorial, but ...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2017.01.019
更新日期:2017-05-01 00:00:00
abstract::The lack of availability of appropriate medicines for children is an extensive and well known problem. As a consequence off label or unlicensed administration of medicinal products in every day paediatric practice is frequent. A variety of obstacles hinder the development of paediatric indications for drugs primarily ...
journal_title:Pharmacological research
pub_type: 社论,评审
doi:10.1016/j.phrs.2011.01.016
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:We examined the influence of diabetes mellitus (DM) on the healing of HCl-induced gastric lesions and the healing promoting effect of IGF-1 on these lesions. METHODS:Experiments were performed on rats injected with streptozotocin (STZ, 70 mg kg(-1), i.p.) 5 weeks prior to the experimental session. Diabetic ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1999.0581
更新日期:2000-02-01 00:00:00
abstract::A favourable option to management symptoms during menopausal transition is menopausal hormone therapy (MHT) but relation among MHT and risk of melanoma is controversial. This study aims to identify, analyse and present the evidence surrounding post-menopausal exogenous hormone therapy and the risk for melanoma in wome...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2020.105182
更新日期:2020-10-01 00:00:00
abstract::Based on the role of ATG7 in the initiation of autophagy, autophagy can be divided into ATG7-dependent selective autophagy and ATG7-independent alternative autophagy. However, the detailed roles of two different types of autophagy in antitumor therapy have not been fully elucidated so far. Here, we for the first time ...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2020.105324
更新日期:2021-01-01 00:00:00
abstract::Disruption of the circadian clock is associated with a variety of human pathologies, including cancer. Rather than being a mere consequence of a global changes associated with the cancer cell transcriptome, the aberrant clock gene expression observed in many tumors may serve for cancer cell survival. This scenario sug...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2015.08.008
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVE:The vasorelaxant effect of 2-arachidonoylglycerol (2-AG) has been well characterised in animals. 2-AG is present in human vascular cells and is up-regulated in cardiovascular pathophysiology. However, the acute vascular actions of 2-AG have not been explored in humans. APPROACH:Mesenteric arteries were obtai...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2014.02.001
更新日期:2014-03-01 00:00:00
abstract::The insulinotropic action of several new esters of succinic acid was assessed in isolated rat islets incubated in the presence of 7 mM D-glucose. An efficient secretory response was observed with the monobenzyl, monoisopropyl, monoallyl, monopropyl, monoethyl, monobutyl, dibutyl, dipropyl and diallyl esters of succini...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1996.0038
更新日期:1996-04-01 00:00:00
abstract::Given the high and increasing prevalence of obesity, the safe and effective treatment of obesity would be beneficial. Here, we examined whether oral hydroxysafflor yellow A (HSYA), an active compound from the dried florets of Carthamus tinctorius L., can reduce high-fat (HF) diet-induced obesity in C57BL/6 J mice. Our...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2018.05.012
更新日期:2018-08-01 00:00:00
abstract:UNLABELLED:The purpose of this study was an attempt to extrapolate favorable observations on the effects of magnesium on platelets and haemostasis from animal models to humans. Intravenous magnesium in the treatment of acute myocardial infarction has been tested in several large clinical trials and remains controversia...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1006/phrs.1997.0212
更新日期:1997-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Thymidylate synthase (TS) expression levels appear to be related to response to 5-fluorouracil-(5-FU)-based chemotherapy in colorectal cancer (CRC) patients. Three polymorphisms have been proposed as modulators of TS expression: a tandemly repeated sequence (2R/3R) in the 5' UTR, a SNP (G>C) w...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2011.04.006
更新日期:2011-09-01 00:00:00
abstract::The synergistic protective effect of nicorandil (KATP channel opener) and amlodipine (calcium channel blocker) on mitochondrial respiration and mitochondrial lipid contents were examined on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for 2 days showed s...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043-6618(03)00223-8
更新日期:2003-12-01 00:00:00
abstract::Epidemiological studies support an inverse correlation between HDL-C and cardiovascular disease. However, low HDL-C levels do not always segregate with premature disease. These include, LCAT deficiency and the apolipoproteinA-IMilano (AIM) variant. AIM has a cysteine for arginine at position 173 in the otherwise cyste...
journal_title:Pharmacological research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.phrs.2016.05.001
更新日期:2016-09-01 00:00:00
abstract::Posttranslational modifications of proteins are important regulatory processes endowing the proteins functional complexity. Over the last decade, numerous studies have shed light on the roles of palmitoylation, one of the most common lipid modifications, in various aspects of neuronal functions. Major players regulati...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2016.06.008
更新日期:2016-09-01 00:00:00
abstract::The endogenous gasotransmitter hydrogen sulphide (H2S) is an important regulator of the cardiovascular system, particularly of myocardial function. Moreover, H2S exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic injury, and is considered an important mediator of "ischemic preconditioning...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/j.phrs.2016.09.006
更新日期:2016-11-01 00:00:00
abstract::Skeletal muscle fitness is vital for human health and disease and is determined by the capacity for burning fuel, mitochondrial ATP production, and contraction. High quality mitochondria in skeletal muscle are essential for maintaining energy homeostasis in response to a myriad of physiologic or pathophysiological str...
journal_title:Pharmacological research
pub_type: 杂志文章,评审
doi:10.1016/j.phrs.2018.12.020
更新日期:2019-03-01 00:00:00
abstract::The effect of flumazenil (FLU) on plasma protein binding of diazepam (DZ), nordiazepam (ND) and oxazepam (OX) was determined in plasma from drug-naive dogs to which graded concentrations of tested drugs alone and in combination were added. The results revealed that as the concentration of FLU added to plasma alone was...
journal_title:Pharmacological research
pub_type: 杂志文章
doi:10.1016/s1043-6618(05)80018-0
更新日期:1995-11-01 00:00:00