Abstract：
:Pirfenidone recently received FDA approval as one of the first two drugs designed to treat idiopathic pulmonary fibrosis. While the clinical data continues to support the efficacy of pirfenidone, the specific molecular mechanism of action of this drug has not been fully defined. From a chemical perspective the comparatively simple and lipophilic structure of pirfenidone combined with its administration at high doses, both experimentally and clinically, complicates some of the basic tenants of drug action and drug design. Our objective here was to identify a commercially available structural mimic of pirfenidone which retains key aspects of its physical chemical properties but does not display any of its antifibrotic effects. We tested these molecules using lung fibroblasts derived from patients with idiopathic pulmonary fibrosis and found phenylpyrrolidine based analogs of pirfenidone that were non-toxic and lacked antifibrotic activity even when applied at millimolar concentrations. Based on our findings, these molecules represent pharmacological tools for future studies delineating pirfenidone's mechanism of action.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Haak AJ,Girtman MA,Ali MF,Carmona EM,Limper AH,Tschumperlin DJdoi
10.1016/j.ejphar.2017.05.050subject
Has Abstractpub_date
2017-09-15 00:00:00pages
87-92eissn
0014-2999issn
1879-0712pii
S0014-2999(17)30382-5journal_volume
811pub_type
杂志文章abstract：:Clinical evidence demonstrates altered glutamatergic neurotransmission in patients suffering from obsessive-compulsive disorder (OCD). We examined the effects of glutamate-related drugs on marble-burying behavior, which is an animal model of OCD. The uncompetitive N-methyl-d-aspartate (NMDA) antagonists memantine (10 ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.01.035
更新日期：2008-05-31 00:00:00
abstract：:Developmental changes in sensitivity of the isolated expansor sedumdariorum muscle of posthatching chicks to noradrenaline (NA), Acetylcholine (ACh) and some other drugs were investigated. This muscle responded to both NA and ACh in early life. The sensitivity to ACh decreased progressively with increasing age and dis...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(75)90135-1
更新日期：1975-08-01 00:00:00
abstract：:Observations of sigma (sigma) receptor heterogeneity have prompted interest in identifying ligands for sigma receptor subtypes. Selective ligands for the sigma-2 are unavailable, but [3H]ifenprodil labels sigma-2 sites. Therefore, isomers and analogues of ifenprodil were compared as potential sigma-2 ligands. Threo-if...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)00763-w
更新日期：1995-02-06 00:00:00
abstract：:The goal of this report is to present the results obtained with three new GABAB receptor antagonists. CGP 54062 has an IC50 in a GABAB binding test of 0.013 microM which is roughly 2500-fold lower than one of the most potent blockers known so far, CGP 35348 (IC50 = 34 microM). CGP 46381 and CGP 36742 have IC50s of 4.9...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90048-m
更新日期：1993-03-23 00:00:00
abstract：:Mutant alph1 subunits of the GABA(A) receptor were coexpressed in combination with the wild-type beta2 and gamma2 subunits in human embryonic kidney (HEK) 293 cells. The binding properties of various benzodiazepine site ligands were determined by displacement of ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00456-7
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abstract：:In this study, we determined the protective potential of trans resveratrol against oxygen-glucose deprivation (OGD) induced reactive oxygen species mediated apoptotic damages in PC12 cells. In vitro model of ischemic cerebral stroke was created by keeping cells in an OGD condition for 6h followed by 24h reoxygenation....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.05.015
更新日期：2011-09-01 00:00:00
abstract：:The relation of the structure of 31 quaternary ammonium compounds (28 inhibitors; 3 substrate analogues) with their effects on the activity of acetylcholinesterase (EC 3.1.1.7; AChE) was studied. The compounds were structurally related to the natural substrate acetylcholine (ACh). All bear a trimethylammonium moiety a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(89)90007-2
更新日期：1989-05-11 00:00:00
abstract：:Previous studies have shown that sertindole (1-[2-[4-[5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl]-1-piperidinyl]ethyl ]-2 imidazolidinone), an atypical antipsychotic drug that is a potent 5-HT2A and dopamine D2 receptor antagonist, preferentially affects mesocorticolimbic rather than mesostriatal dopamine neurons. Usin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00936-4
更新日期：1999-02-12 00:00:00
abstract：:First line antidepressants are the so-called SSRIs (selective serotonin reuptake inhibitors), e.g. fluvoxamine, fluoxetine, sertraline, paroxetine and escitalopram. Unfortunately, these drugs mostly do not provide full symptom relief and have a slow onset of action. Therefore other antidepressants are also being presc...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2014.11.045
更新日期：2015-04-15 00:00:00
abstract：:The activity of a selective tachykinin NK1 receptor antagonist, PD 154075 ([(2-benzofuran)-CH2OCO]-(R)-alpha-MeTrp-(S)-NHCH(CH3) Ph), was examined in radioligand binding studies, in a [Sar9,Met(O2)11]substance P-induced foot-tapping model in the gerbil, and in cisplatin-induced acute and delayed emesis in the ferret. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00950-8
更新日期：1997-02-26 00:00:00
abstract：:Peripheral type benzodiazepine receptors are differentially modified by arachidonate, diethylpyrocarbonate and thiol reagents, as evidenced by the finding that binding of a proposed agonist ([3H]R05-4864) and a proposed antagonist ([3H]PK 11195) to rat kidney mitochondrial membranes can be modified separately. (1) Ara...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90454-7
更新日期：1987-11-17 00:00:00
abstract：:As calcium (Ca2+) channel blockers are effective against the vasoconstrictor responses to 5-hydroxytryptamine (5-HT) in vitro, and a favourable response is claimed for these drugs in migraine prophylaxis, we studied the interaction between nimodipine or nifedipine, and 5-HT for effects on carotid haemodynamics in the ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90773-4
更新日期：1987-04-07 00:00:00
abstract：:3H-Mepyramine (3H-MEP) binds to slide-mounted tissue sections with characteristics indicating the labelling of a H1-histamine receptor. It is saturable (Bmax 12 pg/g tissue), of a high affinity (KD 0.5 mM) and possesses a drug specificity similar to that observed for H1 receptors in a variety of systems. In agreement ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90478-3
更新日期：1979-10-01 00:00:00
abstract：:Angiotensin II receptor number was higher in superior cervical ganglia of 2-week-old when compared to 8-week-old rats. In both young and adult rats, specific binding of [125I][Sar1]angiotensin II was displaced competitively by the AT1-receptor antagonist DuP 753 but not by the AT2-receptor competitor PD 123177. In gan...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(91)90079-w
更新日期：1991-12-12 00:00:00
abstract：:The effects of 2-methylthio ATP, an ATP analogue that is more specific for the P2Y receptor, were investigated on insulin secretion in the anesthetized dog in vivo. 2-Methylthio ATP was infused directly into the pancreaticoduodenal artery for 15 min. The infusion was performed so as to obtain a pancreaticoduodenal art...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90418-9
更新日期：1988-10-11 00:00:00
abstract：:There is experimental evidence indicating that chronic moderate ethanol consumption delays the age-dependent increase in blood pressure. Since the brain natriuretic peptide (BNP) is a potent hypotensive hormone, the effect of chronic ethanol treatment on the heart BNP system was investigated, using spontaneously hyper...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00644-9
更新日期：1996-11-28 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.06.018
更新日期：2015-08-15 00:00:00
abstract：:This paper presents the effect of 14-day intraperitoneal (i.p.) neuroleptic treatment on the behavioural response of Wistar rats to (-)-quinpirole hydrochloride (3 mg/kg, i.p.) administered 24 h after the last neuroleptic dose. Chlorpromazine hydrochloride (10 mg/kg), haloperidol (2 mg/kg) or (+/-)-sulpiride (100 mg/k...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00666-4
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.08.037
更新日期：2004-10-06 00:00:00
abstract：:Previous studies in our laboratory have shown that a hepatotoxic dose of cocaine increases coumarin 7-hydroxylase activity in male DBA/2 mouse liver. In the present study, the dose- and time-dependent responses of the hepatic CYP2A4/5 complex to cocaine-induced liver damage were studied. Cocaine increased CYP2A4/5 lev...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(94)90026-4
更新日期：1994-11-01 00:00:00
abstract：:The intrathecal injection of a variety of selective kappa-opioid receptor ligands did not result in significant inhibition of thermal nociceptive tail flick responses in rats. In contrast, these compounds dose dependently inhibited pressure nociceptive responses. Cross-tolerance studies revealed that the kappa-opioid ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90223-8
更新日期：1987-06-04 00:00:00
abstract：:Potentiation by neuropeptide Y of serotonin (5-HT)-induced vasoconstriction was investigated in porcine coronary artery. 5-HT caused concentration-dependent contraction through 5-HT2A receptors. Neuropeptide Y (30 nM) significantly increased the 5HT-induced contraction by 16+/-5% in arteries with intact endothelium. R...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.06.036
更新日期：2006-08-21 00:00:00
abstract：:Increasing evidence indicates that brain inflammation is involved in the pathogenesis of neuropsychiatric diseases. Mast cells (MCs) are located perivascularly close to neurons and microglia, primarily in the leptomeninges, thalamus, hypothalamus and especially the median eminence. Corticotropin-releasing factor (CRF)...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2015.03.086
更新日期：2016-05-05 00:00:00
abstract：:The effects of cannabinoid drugs on cAMP production were examined in mammalian brain. The cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrrolo[1,2,3,-d,e-1,4-benzoxazin-6-yl]-(1-naphthalenyl) methanone (WIN55,212-2) decreased forskolin-induced cAMP accumulation in a concentration...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)01575-3
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abstract：:Mangiferin, a glucosylxanthone from Mangifera indica, has been reported to have anti-inflammatory effects. However, the protective effects and mechanisms of mangiferin on liver injury remain unclear. This study aimed to determine the protective effects and mechanisms of mangiferin on lipopolysaccharide (LPS) and D-gal...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.12.006
更新日期：2016-01-05 00:00:00
abstract：:We tested the hypothesis that relaxation of the rat mesenteric artery in response to insulin is mediated by K(+) channels. Two concentrations of insulin (10 and 100 mU/ml) induced relaxation of the artery by 6+/-1%, 24+/-3% (mean+/-S.E.M.). Denudation of the endothelium or precontraction by KCl (30 mM), clotrimazole (...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00892-x
更新日期：2001-01-05 00:00:00
abstract：:Sodium nitroprusside produced a dose-dependent increase in extracellular levels of cGMP in the cerebellar cortex in vivo. This was independent of nitric oxide synthase activity. The metalloporphyrins zinc-protoporphyrin-IX, tin-protoporphyrin-IX and zinc-deuteroporphyrin-IX,2,4-bis glycol prevented the increase in cGM...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(94)90149-x
更新日期：1994-05-17 00:00:00
abstract：:Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that contracts most smooth muscles. Although S1P has been shown to contract bladder smooth muscle, the mechanism(s) by which S1P initiates contraction has not been extensively investigated. The goal of this study was to determine if S1P-induced force generation...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.10.004
更新日期：2013-11-15 00:00:00
abstract：:The putative imidazoline I(3) receptor antagonist 2-(2-ethyl-2,3-dihydrobenzo[b]furan-2-yl)-1H-imidazole (KU14R) has been shown to block the effects of the atypical I(3) agonist efaroxan at the level of the ATP-sensitive K(+) (K(ATP)) channel in isolated pancreatic islet beta cells, but its effects in vivo are not kno...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)02473-1
更新日期：2002-11-01 00:00:00
abstract：:Neuropeptide Y has direct vasoconstrictor actions and potentiates the effects of other vasoconstrictor agents. To find out whether both effects of neuropeptide Y are mediated via the same receptor and intracellular mechanism, the interaction between neuropeptide Y and angiotensin II was studied in rabbit femoral arter...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)00619-i
更新日期：1995-01-05 00:00:00
