Interaction of progesterone derivatives with the digitalis target enzyme: impact of glycosidation on inhibitory potency.


:As a function of the structural modification of the steroid nucleus, the inhibitory interaction of 11 progesterone derivatives with human Na/K-ATPase (Na+/K(+)-transporting ATPase, EC, through C3-O-rhamnosylation, is either much decreased or weakly up to strongly increased, so that the rhamnosyl residue contributes to the complementary Gibbs energy of interaction, at the most, the same Gibbs energy increment as realized in ouabain. After C3 beta-O-rhamnosylation, the activity of some progesterone derivatives considerably surpasses that of 3 beta-O-rhamnosyl-chlormadinolacetate, which has been known to elicit positive inotropy in cats. The progesterone derivatives (aglycons and glycosides), that have been analysed more closely, produce their effects by the same molecular mechanism of interaction with Na/K-ATPase as characteristic for digitalis aglycons and glycosides. The results promise to pave the way for the identification of the chemical nature of endogenous digitalis and for the design of novel inotropic drugs.


Pharmacol Res


Pharmacological research


Weiland J,Schönfeld W,Menke KH,Repke KR




Has Abstract


1991-01-01 00:00:00














  • GDF-11 prevents cardiomyocyte hypertrophy by maintaining the sarcoplasmic reticulum-mitochondria communication.

    abstract::Growth differentiation factor 11 (GDF11) is a novel factor with controversial effects on cardiac hypertrophy both in vivo and in vitro. Although recent evidence has corroborated that GDF11 prevents the development of cardiac hypertrophy, its molecular mechanism remains unclear. In our previous work, we showed that nor...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Garrido-Moreno V,Díaz-Vegas A,López-Crisosto C,Troncoso MF,Navarro-Marquez M,García L,Estrada M,Cifuentes M,Lavandero S

    更新日期:2019-08-01 00:00:00

  • Imiquimod-induced psoriasis-like skin inflammation is suppressed by BET bromodomain inhibitor in mice through RORC/IL-17A pathway modulation.

    abstract::Psoriasis is one of the most common skin disorders characterized by erythematous plaques that result from hyperproliferative keratinocytes and infiltration of inflammatory leukocytes into dermis and epidermis. Recent studies suggest that IL-23/IL-17A/IL-22 cytokine axis plays an important role in the pathogenesis of p...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Nadeem A,Al-Harbi NO,Al-Harbi MM,El-Sherbeeny AM,Ahmad SF,Siddiqui N,Ansari MA,Zoheir KM,Attia SM,Al-Hosaini KA,Al-Sharary SD

    更新日期:2015-09-01 00:00:00

  • Uncariitannin, a polyphenolic polymer from Uncaria gambier, attenuates Staphylococcus aureus virulence through an MgrA-mediated regulation of α-hemolysin.

    abstract::A global transcriptional regulator, MgrA, was previously identified as a key determinant of virulence in Staphylococcus aureus. An 80% EtOH extract of Uncaria gambier was found to attenuate the virulence of S. aureus via its effects on MgrA. Using bioassay-guided fractionation, a polyphenolic polymer, uncariitannin, w...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Zhang H,Jiang JM,Han L,Lao YZ,Zheng D,Chen YY,Wan SJ,Zheng CW,Tan HS,Li ZG,Xu HX

    更新日期:2019-09-01 00:00:00

  • Long noncoding RNA AK039312 and AK079370 inhibits bone formation via miR-199b-5p.

    abstract::Osteoporosis caused by aging and menopause had become an emerging threat to human health. The reduction of osteoblast differentiation has been considered to be an essential cause of osteoporosis. Osteoblast differentiation could be regulated by LncRNAs, and increasing evidences have proved that LncRNAs may be adopted ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Yin C,Tian Y,Yu Y,Li D,Miao Z,Su P,Zhao Y,Wang X,Pei J,Zhang K,Qian A

    更新日期:2021-01-01 00:00:00

  • Tumor deconstruction as a tool for advanced drug screening and repositioning.

    abstract::A major focus of contemporary drug screening strategies is the identification of novel anticancer compounds, which often results in underutilization of resources. Current drug evaluation involves in vivo tumor (xenograft) regression as proof-of-principle for cytotoxicity (POC). However, this end-point lacks any assess...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Naik RR,Luo T,Kohandel M,Bapat SA

    更新日期:2016-09-01 00:00:00

  • Antiplatelet and antithrombotic activities of essential oil from wild Ocotea quixos (Lam.) Kosterm. (Lauraceae) calices from Amazonian Ecuador.

    abstract::Ocotea quixos essential oil was shown to possess significant inhibitory activity of platelet aggregation and clot retraction in rodent plasma. This study is aimed at fully characterizing the antiplatelet activity of the whole essential oil and its main components trans-cinnamaldehyde and methyl cinnamate also in human...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Ballabeni V,Tognolini M,Bertoni S,Bruni R,Guerrini A,Rueda GM,Barocelli E

    更新日期:2007-01-01 00:00:00

  • Cinnamaldehyde in diabetes: A review of pharmacology, pharmacokinetics and safety.

    abstract::Cinnamaldehyde, one of the active components derived from Cinnamon, has been used as a natural flavorant and fragrance agent in kitchen and industry. Emerging studies have been performed over the past decades to evaluate its beneficial role in management of diabetes and its complications. This review highlights recent...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Zhu R,Liu H,Liu C,Wang L,Ma R,Chen B,Li L,Niu J,Fu M,Zhang D,Gao S

    更新日期:2017-08-01 00:00:00

  • Temsirolimus promotes autophagic clearance of amyloid-β and provides protective effects in cellular and animal models of Alzheimer's disease.

    abstract::Accumulation of amyloid-β peptides (Aβ) within brain is a major pathogenic hallmark of Alzheimer's disease (AD). Emerging evidence suggests that autophagy, an important intracellular catabolic process, is involved in Aβ clearance. Here, we investigated whether temsirolimus, a newly developed compound approved by Food ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Jiang T,Yu JT,Zhu XC,Tan MS,Wang HF,Cao L,Zhang QQ,Shi JQ,Gao L,Qin H,Zhang YD,Tan L

    更新日期:2014-03-01 00:00:00

  • Insulinotropic action of novel succinic acid esters.

    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


    authors: Björkling F,Malaisse-Lagae F,Malaisse WJ

    更新日期:1996-04-01 00:00:00

  • Broad impact of deleting endogenous cannabinoid hydrolyzing enzymes and the CB1 cannabinoid receptor on the endogenous cannabinoid-related lipidome in eight regions of the mouse brain.

    abstract:BACKGROUND AND PURPOSE:The enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) hydrolyze endogenous cannabinoids (eCBs), N-arachidonoyl ethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG), respectively. These enzymes also metabolize eCB analogs such as lipoamines and 2-acyl glycerols, most of...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Leishman E,Cornett B,Spork K,Straiker A,Mackie K,Bradshaw HB

    更新日期:2016-08-01 00:00:00

  • 2-arachidonyl-glycerol stimulates nitric oxide release from human immune and vascular tissues and invertebrate immunocytes by cannabinoid receptor 1.

    abstract::The pharmacological physiological effects of the endogenous cannabinomimetic (endocannabinoid) anandamide have been well characterized. Another endocannabinoid, 2-arachidonoyl-glycerol (2-AG), has been less-widely studied. 2-AG occurs in vertebrate and invertebrate tissues and binds to both cannabinoid receptors (CB1 ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Stefano GB,Bilfinger TV,Rialas CM,Deutsch DG

    更新日期:2000-10-01 00:00:00

  • Vigabatrin does not affect the intestinal absorption of phenytoin in rat duodeno-jejunal loops in situ.

    abstract::The antiepileptic drug vigabatrin (GVG) is known to decrease significantly the serum concentration of concurrently administered phenytoin (PHT) in epileptic patients. To assess a possible mechanism for this interaction, the effect of GVG on the intestinal absorption of PHT was investigated by means of circulation expe...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Tonini M,Gatti G,Manzo L,Olibet G,Coccini T,Perucca E

    更新日期:1992-09-01 00:00:00

  • Free radicals and antioxidant status following pylorus ligation induced gastric mucosal injury in rats.

    abstract::The present investigation was undertaken to suggest the involvement of free radicals in the pathogenesis of pyloric ligation induced ulcers in rats. Lipid peroxidation product (MDA), antioxidant contents and secretory activity have been studied in the rat stomach at different time intervals after pylorus ligation indu...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Rastogi L,Patnaik GK,Dikshit M

    更新日期:1998-08-01 00:00:00

  • Cyproterone acetate and reversal of the impaired endometrial decidualization in streptozotocin-diabetic pseudopregnant rats.

    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


    authors: Zakaria R,Ismail Z,Chatterjee A

    更新日期:2000-08-01 00:00:00

  • Antinociceptive and antiinflammatory activities of Artemisia copa extracts.

    abstract::The aqueous extract from aerial parts of Artemisia copa Phil. (Compositae), was evaluated for antinociceptive activity using writhing, formalin, and hot-plate tests in mice. A dose-related antinociceptive response was obtained in the writhing test at doses of 500 and 1000 mg/kg p.o. (percentage of inhibition 23.3 and ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Miño J,Moscatelli V,Hnatyszyn O,Gorzalczany S,Acevedo C,Ferraro G

    更新日期:2004-07-01 00:00:00

  • Molecular modeling study on resistance of WT/D473H SMO to antagonists LDE-225 and LEQ-506.

    abstract::The smoothened (SMO) receptor, an essential signal transducer in the Hedgehog pathway, was targeted with antagonists to suppress the tumor. It is interesting that SMO D473H mutation confers resistance on inhibitor LDE-225 rather than LEQ-506. In this paper, the binding modes of them against the wild type and mutant SM...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Tu J,Li JJ,Song LT,Zhai HL,Wang J,Zhang XY

    更新日期:2018-03-01 00:00:00

  • Flumazenil, diazepam, nordiazepam and oxazepam interactions on plasma protein binding.

    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


    authors: Wala EP,Sloan JW

    更新日期:1995-11-01 00:00:00

  • The influence of lidocaine and verapamil on haemodynamic parameters after intravenous administration of midazolam in rabbits.

    abstract::Cardiac arrhythmia can be a serious complication during general anaesthesia of patients suffering from cardiac arrhythmias and using antiarrhythmic drugs. The aim of the present experiments was to establish the way in which lidocaine and verapamil influence haemodynamic parameters of rabbits after midazolam anaesthesi...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Wiktorowska A,Owczarek J,Orszulak-Michalak D

    更新日期:1999-06-01 00:00:00

  • In vitro physiological evidence of enhanced antioxidant and neuroprotective action of 2,3-dihydromelatonin, a melatonin analogue.

    abstract::As the capacity of the endogenous antioxidative system is limited, pharmacological treatment with antioxidants may help to protect neuronal tissue against increased amount of reactive oxygen species produced during oxidative stress. We attempted to improve resistance of rat hippocampal slices exposed to ischaemia in v...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Gáspárová Z,Stolc S,Snirc V

    更新日期:2006-01-01 00:00:00

  • Hydralazine improves ischemia-induced neovasculogenesis via xanthine-oxidase inhibition in chronic renal insufficiency.

    abstract::Oxidative stress is related to the progression of renal diseases and modulation of oxidative stress can lead to a reduction in vascular events in patients with chronic renal insufficiency (CRI). Indoxyl sulfate (IS) and xanthine oxidase (XO) are related to impaired neovasculogenesis in CRI. Hydralazine is suggested fo...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Chang TT,Chen JW

    更新日期:2020-01-01 00:00:00

  • The abundance of the long intergenic non-coding RNA 01087 differentiates between luminal and triple-negative breast cancers and predicts patient outcome.

    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


    authors: De Palma FDE,Del Monaco V,Pol JG,Kremer M,D'Argenio V,Stoll G,Montanaro D,Uszczyńska-Ratajczak B,Klein CC,Vlasova A,Botti G,D'Aiuto M,Baldi A,Guigó R,Kroemer G,Maiuri MC,Salvatore F

    更新日期:2020-11-01 00:00:00

  • MicroRNA-128-3p aggravates doxorubicin-induced liver injury by promoting oxidative stress via targeting Sirtuin-1.

    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


    authors: Zhao X,Jin Y,Li L,Xu L,Tang Z,Qi Y,Yin L,Peng J

    更新日期:2019-08-01 00:00:00

  • Hypolipidaemic activity in rodents of boron analogs of phosphonoacetates and cyanoborane adducts of dialkyl aminomethylphosphonates.

    abstract::Boron analogues of phosphonoacetates proved to be potent hypolipidaemic agents in rodents, lowering both serum cholesterol and triglyceride levels. (C2H5O)3PBH2COOCH3 proved to be the most effective agent in mice, lowering serum cholesterol 46% and serum triglycerides 54% after 16 days. (C2H5O)3PBH2COOH and Na+H+(C2H5...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Hall IH,Wong OT,Sood A,Sood CK,Spielvogel BF,Shrewsbury RP,Morse KW

    更新日期:1992-04-01 00:00:00

  • Transcriptome profiling of NIH3T3 cell lines expressing opsin and the P23H opsin mutant identifies candidate drugs for the treatment of retinitis pigmentosa.

    abstract::Mammalian cells are commonly employed in screening assays to identify active compounds that could potentially affect the progression of different human diseases including retinitis pigmentosa (RP), a class of inherited diseases causing retinal degeneration with compromised vision. Using transcriptome analysis, we comp...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Chen Y,Brooks MJ,Gieser L,Swaroop A,Palczewski K

    更新日期:2017-01-01 00:00:00

  • Funny channels in the control of cardiac rhythm and mode of action of selective blockers.

    abstract::"Funny" (f) channels underlie the cardiac "pacemaker"I(f) current, originally described as an inward current activated on hyperpolarization to the diastolic range of voltages in sino-atrial node myocytes [Brown, HF, DiFrancesco, D, Noble, SJ. How does adrenaline accelerate the heart? Nature 1979;280:235-236]. The invo...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: DiFrancesco D

    更新日期:2006-05-01 00:00:00

  • Role of aldehyde dehydrogenase in the biological activity of spermine dialdehyde, a novel immunosuppressive/purging agent.

    abstract::The antitumour and immunosuppressive activities of spermine dialdehyde (SDA), a synthetic, oxidized form of spermine, were examined using L1210 cell lines and murine bone marrow cells. SDA acted as a high affinity substrate for aldehyde dehydrogenase (ADH) derived from different sources, with kinetic profiles similar ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Kazmi SM,Li D,Koop K,Conant J,Lau CY

    更新日期:1992-05-01 00:00:00

  • From stroke to neurodegenerative diseases: The multi-target neuroprotective effects of 3-n-butylphthalide and its derivatives.

    abstract::Discovering effective agents to slow or stop neurodegeneration is a challenging task. Over decades, only a few drugs were approved by Food and Drug Administration (FDA) and most ended in failure. The lessons learned have switched the strategy of drug discovery from designing highly selective ligands to a network pharm...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Huang L,Wang S,Ma F,Zhang Y,Peng Y,Xing C,Feng Y,Wang X,Peng Y

    更新日期:2018-09-01 00:00:00

  • N3,N7-diaminophenothiazinium derivatives as antagonists of α7-nicotinic acetylcholine receptors expressed in Xenopus oocytes.

    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 Xe...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Sadek B,Ashoor A,Al Mansouri A,Lorke DE,Nurulain SM,Petroianu G,Wainwright M,Oz M

    更新日期:2012-09-01 00:00:00

  • Disease modifying therapies in type 1 diabetes: Where have we been, and where are we going?

    abstract::With more than four decades of clinical research and 25 years of clinical trials, much is known about the natural history of T1D before and after clinical diagnosis. We know that autoimmunity occurs early in life, that islet autoimmunity inevitably leads to clinically overt disease, and that some immune therapies can ...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Lord S,Greenbaum CJ

    更新日期:2015-08-01 00:00:00

  • Short-term effects of Poly(I:C) on gut permeability.

    abstract::The intestinal barrier function depends on an adequate response to pathogens by the epithelium. Toll-like receptor 3 (TLR-3) recognizes double-stranded RNA, a virus-associated molecular pattern. Activation of TLR-3 with Poly(I:C), a synthetic agonist, modulates tissue repair and permeability in other epithelia; howeve...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Moyano-Porcile V,Olavarría-Ramírez L,González-Arancibia C,Bravo JA,Julio-Pieper M

    更新日期:2015-11-01 00:00:00