Archiv für Experimentelle Pathologie und Pharmakologie (N-S ARCH PHARMACOL)

Publisher: Springer Verlag

Journal description

Naunyn-Schmiedeberg's Archives of Pharmacology was founded in 1873 as "Archiv für experimentelle Pathologie und Pharmakologie" by B. Naunyn O. Schmiedeberg E. Klebs. In cooperation with colleagues it was edited by L. Krehl W. Straub W. Heubner and others; from Vol. 208 No. 2 on edited in cooperation with the Deutsche Pharmakologische Gesellschaft. Vols. 1-158 (1930) Leipzig F.C.W. Vogel Vols. 159-196 (1940) Berlin F.C.W. Vogel; from Vol. 197 on Berlin Springer. Vols. 110 to 253 "Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie"; from Vol. 254 (1966) to 263 "Naunyn-Schmiedebergs Archiv für Pharmakologie und experimentelle Pathologie"; from Vol. 264 (1969) to 271 "Naunyn-Schmiedebergs Archiv für Pharmakologie"; from Vol. 272 (1972) "Naunyn-Schmiedeberg's Archives of Pharmacology". As of Vol. 343 (1991) edited on behalf of the Deutsche Gesellschaft für Pharmakologie und Toxikologie; from Vol. 349 (1994) Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie e.V.

Current impact factor: 2.47

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 Impact Factor 2.471
2013 Impact Factor 2.36
2012 Impact Factor 2.147
2011 Impact Factor 2.647
2010 Impact Factor 2.5
2009 Impact Factor 2.631
2008 Impact Factor 2.83
2007 Impact Factor 2.161
2006 Impact Factor 2.779
2005 Impact Factor 2.098
2004 Impact Factor 1.963
2003 Impact Factor 2.101
2002 Impact Factor 2.566
2001 Impact Factor 2.472
2000 Impact Factor 2.869
1999 Impact Factor 2.414
1998 Impact Factor 2.2
1997 Impact Factor 2.492
1996 Impact Factor 2.679
1995 Impact Factor 3.04
1994 Impact Factor 2.813
1993 Impact Factor 3
1992 Impact Factor 3.227

Impact factor over time

Impact factor

Additional details

5-year impact 2.33
Cited half-life >10.0
Immediacy index 0.62
Eigenfactor 0.00
Article influence 0.58
Website Naunyn-Schmiedeberg's Archives of Pharmacology website
Other titles Naunyn-Schmiedeberg's archives of pharmacology (Online), Archives of pharmacology
ISSN 0028-1298
OCLC 43450808
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Springer Verlag

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    • Author's post-print on any open access repository after 12 months after publication
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    • Set phrase to accompany link to published version (see policy)
    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPases, causes slowly developing and subsequently diminishing characteristic contractions in vascular smooth muscle, and the second application of CPA has incompletely repeatable effects, depending on the vessel type. The objective of the present study was to examine the mechanisms underlying the significant decrease of CPA-induced contractions upon the second application. A pharmacological intervention of Ca2+ extrusion process as a strategy was performed to modulate vasoconstrictor effects of CPA in rat aortic ring preparations. CPA-induced contractions, expressed as percentages of the contractions induced by KCl (80 mM), were significantly decreased from 44.1 ± 5.7 to 7.6 ± 1.8 % (P < 0.001) upon the second application. The contractions, however, were completely repeatable in the presence of vanadate, an inhibitor of ATPases, but not of ouabain, an inhibitor of Na+-pumps. Strikingly, CPA-induced contractions were sustained and completely repeatable in Na+-free and low Na+ medium. Furthermore, we found that the contractions were completely repeatable in the presence of 2′,4′-dichlorobenzamil, an inhibitor of the forward mode of Na+/Ca2+ exchangers, but not of KBR7943, an inhibitor of the reverse mode of Na+/Ca2+ exchangers. Our findings indicate that CPA by inducing a transient rise in cytosolic Ca2+ level causes a long-lasting upregulation of plasma membrane (PM) Ca2+ extruders and thus leads to a diminished contraction upon its second application in blood vessels. This suggests that there is a functional coupling between PM Ca2+ extruders and SR Ca2+-ATPases in rat aortic smooth muscle cells.
    No preview · Article · Feb 2016 · Archiv für Experimentelle Pathologie und Pharmakologie
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    ABSTRACT: Retigabine is a new antiepileptic drug with the main mechanism of action: activation of voltage-gated potassium channels (Kv7) represented in many tissues including the excitable cells—neuronal and muscular. The aim of this article is to determine the role of potassium channels located on the skeletal muscle membrane in the in vivo and in vitro reduction of muscle contractile activity induced by retigabine. We studied the effects of retigabine on the motor function in vivo using a bar holding test and exploratory activity using open field test in rats. Electrical field stimulation (EFS) was applied to skeletal muscle strips in vitro in order to evaluate muscular activity. We registered a significant decrease in the muscle tone and exploratory activity of rats, treated orally with 60 mg/kg bw retigabine. In vitro experiments showed decrease in the maximal muscle force of strips in the presence of retigabine in the medium after both indirect (nerve-like) and direct (muscle-like) stimulation. The effects were fully antagonized by XE-991 (Kv7 channel blocker), which supports our hypothesis about the relation between these types of potassium channels and the observed change in the muscle force. Based on these results, we can conclude that skeletal muscle Kv7 channels play a significant role in the myorelaxation and reduced muscle force registered after treatment with Kv7 channels openers (e.g., retigabine). The hyperpolarization of skeletal muscle membrane caused by accelerated K+ efflux may be the underlying cause for the effect of retigabine on the muscle tone.
    No preview · Article · Jan 2016 · Archiv für Experimentelle Pathologie und Pharmakologie
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    ABSTRACT: Diminazene aceturate (DA) is the active component of some trypanocidal drugs used for the treatment of animals infected with trypanosomosis and babesiosis. Residues of DA may cause hepatotoxic and nephrotoxic effects. Therefore, the purpose of this study was to investigate the occurrence of oxidative stress, i.e., changes in the antioxidant defense system of rats treated with a single dose of 3.5 mg kg−1 of DA. All treatments were intramuscularly administered, and evaluations were performed on days 7 and 21 post-treatment (PT). Liver and kidney samples were collected and evaluated by histopathology and oxidative stress parameters (thiobarbituric acid-reactive species, catalase, superoxide dismutase, carbonyl, non-protein thiols, and reduced glutathione). Finally, blood was collected to determine seric DA concentration. Superoxide dismutase (SOD) and catalase (CAT) activities in liver and kidney of rats were dramatically inhibited (p < 0.05) compared to the control group on day 21 PT. This difference is related to the concomitant increase (p < 0.05) in malondialdehyde (MDA) content, which was identified by an increase in thiobarbituric acid-reactive species (TBARS) levels. The carbonyl levels did not differ between groups (p > 0.05). Both non-protein thiols (NPSH) and glutathione (GSH) levels in liver and kidney decreased (p < 0.05) on day 21 PT. Chromatographic analyses showed lower levels of DA on day 21 PT compared to day 7 PT. A negative correlation was observed between DA concentration in serum and lipid peroxidation in liver and kidney tissues on 21 days PT. Histopathology revealed vacuolar degeneration in liver and kidney samples on day 21 PT. Our findings indicate that DA could cause oxidative damage to liver and kidney of rats.
    No preview · Article · Jan 2016 · Archiv für Experimentelle Pathologie und Pharmakologie
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    ABSTRACT: Nonalcoholic steatohepatitis (NAFLD) is a progressive form of liver disease that leads to advanced fibrosis. The present study was designed to assess the hepatoprotective effect of thymoquinone (TQ) on liver functions, insulin resistance, and PPAR-γ expression in NAFLD. Rats were divided into two main groups: one fed with normal rat chow diet and the other with high-fat high-cholesterol diet group for 6 weeks. Every group was subdivided into three subgroups (n = 8): treated with saline, low dose TQ (10 mg/kg), high dose TQ (20 mg/kg). High fat high cholesterol diet caused marked liver damage as noted in histopathology and significant increase in liver index, liver enzymes. There was significant increase in the insulin resistance, serum cholesterol, triglyceride, PPAR-γ gene overexpression with significant decrease in HDL. Additionally, oxidative stress increased by measuring MDA associated with significant decrease in serum total antioxidant capacity. As markers of inflammation, hepatic TNF-α was significantly increased with decrease in IL10. Further, there was increase in BAX protein with decrease in Bcl as compared to control group. This model of 6 weeks high-fat high-cholesterol diet showed minimal fibrosis as noticed by increase MMP2 and Masson trichrome satin. Co-treatment with TQ improved all previous parameters. High dose was more effective, although mostly non-statistically significant. TQ may have a promising agent to improve hepatic steatosis, oxidative stress; inflammatory, apoptotic status, fibrosis and so prevent liver damage in patients with NAFLD. Although PPAR-γ was significantly under-expressed by TQ, insulin resistance was improved significantly suggesting a role of liver damage.
    No preview · Article · Jan 2016 · Archiv für Experimentelle Pathologie und Pharmakologie
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    ABSTRACT: Based on clinical studies regarding the beneficial effect of gabapentin in depression, we aimed to evaluate the antidepressant-like properties of gabapentin in mice and also the participation of nitric oxide (NO)/cyclic guanosine monophosphate pathway in this effect. The following drugs were used in this study: gabapentin; N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific NO synthase (NOS) inhibitor; 7-nitroindazole, a specific neuronal NOS inhibitor; aminoguanidine, a specific inducible NOS inhibitor; L-arginine, a NO precursor; and sildenafil, a phosphodiestrase inhibitor. Finally, we studied the behavioral effects through the forced swimming test (FST) and the changes of the hippocampus NO level through nitrite assay. The immobility time was significantly reduced after gabapentin administration. Co-administration of non-effective doses of gabapentin and L-NAME or 7-nitroindazole (7-NI) resulted in antidepressant-like effect in FST, while aminoguanidine did not affect the immobility time of gabapentin-treated mice. Furthermore, the antidepressant-like property of gabapentin was prevented by L-arginine or sildenafil. Also, the hippocampal nitrite level was significantly lower in gabapentin-treated mice relative to saline-injected mice, and co-administration of 7-NI with sub-effective gabapentin caused a significant decrease in hippocampal nitrite levels. Our results indicate that the antidepressant-like effect of gabapentin in the mice FST model is mediated at least in part through nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.
    No preview · Article · Jan 2016 · Archiv für Experimentelle Pathologie und Pharmakologie
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    ABSTRACT: The aim of this study was to evaluate whether the sub-chronic systemic ethanol exposure has direct effect on cavernosal smooth muscle contractions induced by KCl (depolarizing) and phenylephrine (α1-receptor agonist), and the possible involvement of RhoA/Rho-kinase pathway. Sub-chronic systemic ethanol was applied to mice with inhalation route for 14 days. The blood levels in ethanol-treated mice averaged 121.2 ± 9.1 mg/dl. KCl (80 mM) and phenylephrine (10 nM-100 μM) induced sustained contractions in corpus corporal strips from sham-treated mice. Sub-chronic ethanol treatment reduced the contractions to KCl. However, phenylephrine-induced contractions were not affected by ethanol treatment. Rho-kinase inhibitor fasudil (50 μM) and Y-27632 (50 μM) inhibited contractions to KCl and phenylephrine in sham-treated mice. Ethanol treatment increased the inhibitory effect of Rho-kinase inhibitors on contractions to phenylephrine. The relaxations induced by fasudil (100 μM) and Y-27632 (500 μM) did not change in ethanol treatment group. In ethanol-treated group, the expression of RhoA decreased compared to sham-treated group. Also, ROCK1 expression was reduced by ethanol but not statically significant to sham-treated group; however, the expression of ROCK2 increased in ethanol group. From these findings, it seems that phenylephrine and KCl-induced contractions depends on RhoA/Rho-kinase-mediated Ca(2+) sensitization. Also, these results suggest that the ethanol treatment decreased the expression of RhoA, and the inhibitory effect of ethanol on KCl-induced contractions may be due to, at least in part, the inhibition of a RhoA/Rho-kinase in mouse corpus cavernosum.
    No preview · Article · Jan 2016 · Archiv für Experimentelle Pathologie und Pharmakologie
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    ABSTRACT: Dipyridamole (DYP) is an anti-platelet agent with marked vasodilator, anti-oxidant, and anti-inflammatory activity. The present study investigated the role of adenosine receptors in DYP-mediated protection against ischemia reperfusion-induced acute kidney injury (AKI) in rats. The rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h. The renal damage induced by ischemia reperfusion injury (IRI) was assessed by measuring creatinine clearance, blood urea nitrogen, uric acid, plasma potassium, fractional excretion of sodium, and microproteinuria in rats. The oxidative stress in renal tissues was assessed by quantification of thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The hematoxylin-eosin staining was carried out to observe histopathological changes in renal tissues. DYP (10 and 30 mg/kg, intraperitoneal, i.p.) was administered 30 min before subjecting the rats to renal IRI. In separate groups, caffeine (50 mg/kg, i.p.), an adenosinergic A1 and A2A receptor antagonist was administered with and without DYP treatment before subjecting the rats to renal IRI. The ischemia reperfusion-induced AKI was demonstrated by significant changes in serum as well as urinary parameters, enhanced oxidative stress, and histopathological changes in renal tissues. The administration of DYP demonstrated protection against AKI. The prior treatment with caffeine abolished DYP-mediated reno-protection suggesting role of A1 and A2A adenosine receptors in DYP-mediated reno-protection in rats. It is concluded that adenosine receptors find their definite involvement in DYP-mediated anti-oxidative and reno-protective effect against ischemia reperfusion-induced AKI.
    No preview · Article · Jan 2016 · Archiv für Experimentelle Pathologie und Pharmakologie
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    ABSTRACT: The aim of the present work was to investigate possible protective effects of febuxostat, a highly potent xanthine oxidase inhibitor, against acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats. Male Sprague Dawley rats were randomly divided into six groups, as follows: (i) vehicle control group; (ii) and (iii) febuxostat 10 and febuxostat 15 groups, drug-treated controls; (iv) LPS group, receiving an intraperitoneal injection of LPS (7.5 mg/kg); (v) and (vi) febuxostat 10-LPS and febuxostat 15-LPS groups, receiving oral treatment of febuxostat (10 and 15 mg/kg/day, respectively) for 7 days before LPS. After 18 h administration of LPS, blood was collected for C-reactive protein (CRP) measurement. Bronchoalveolar lavage fluid (BALF) was examined for leukocyte infiltration, lactate dehydrogenase (LDH) activity, protein content, and total nitrate/nitrite. Lung weight gain was determined, and lung tissue homogenate was prepared and evaluated for oxidative stress. Tumor necrosis factor-α (TNF-α) was assessed in BALF and lung homogenate. Moreover, histological changes of lung tissues were evaluated. LPS elicited lung injury characterized by increased lung water content (by 1.2 fold), leukocyte infiltration (by 13 fold), inflammation and oxidative stress (indicated by increased malondialdehyde (MDA), by 3.4 fold), and reduced superoxide dismutase (SOD) activity (by 34 %). Febuxostat dose-dependently decreased LPS-induced lung edema and elevations in BALF protein content, infiltration of leukocytes, and LDH activity. Moreover, the elevated levels of TNF-α in BALF and lung tissue of LPS-treated rats were attenuated by febuxostat pretreatment. Febuxostat also displayed a potent antioxidant activity by decreasing lung tissue levels of MDA and enhancing SOD activity. Histological analysis of lung tissue further demonstrated that febuxostat dose-dependently reversed LPS-induced histopathological changes. These findings demonstrate a significant dose-dependent protection by febuxostat against LPS-induced lung inflammation in rats.
    No preview · Article · Dec 2015 · Archiv für Experimentelle Pathologie und Pharmakologie
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    ABSTRACT: Propofol and dexmedetomidine are very commonly used sedative agents. However, several case reports demonstrated cardiovascular adverse effects of these two sedatives. Both substances were previously demonstrated to quite potently inhibit neuronal voltage-gated Na(+) channels. Thus, a possible molecular mechanism for some of their cardiac side effects is an inhibition of cardiac voltage gated Na(+) channels. In this study, we therefore explored the effects of propofol and dexmedetomidine on the cardiac predominant Na(+) channel α-subunit Nav1.5. Effects of propofol and dexmedetomidine were investigated on constructs of the human α-subunit Nav1.5 stably expressed in HEK-293 cells by means of whole-cell patch clamp recordings. Both agents induced a concentration-dependent tonic inhibition of Nav1.5. The calculated IC50 value for propofol was 228 ± 10 μM, and for dexmedetomidine 170 ± 20 μM. Tonic block only marginally increased on inactivated channels, and a weak use-dependent block at 10 Hz was observed for dexmedetomidine (16 ± 2 % by 100 μM). The voltage dependencies of fast and slow inactivation as well as the time course of recovery from inactivation were shifted by both propofol and dexmedetomidine. Propofol (IC50 126 ± 47 μM) and dexmedetomidine (IC50 182 ± 27 μM) blocked the persistent sodium current induced by veratradine. Finally, the local-anesthetic (LA)-insensitive mutant Nav1.5-F1760A exhibited reduced tonic and use-dependent block by both substances. Dexmedetomidine was generally more potent as compared to propofol. Propofol and dexmedetomidine seem to interact with the LA-binding site to inhibit the cardiac Na(+) channel Nav1.5 in a state-dependent manner. These data suggest that Nav1.5 is a hitherto unrecognized molecular component of some cardiovascular side effects of these sedative agents.
    No preview · Article · Dec 2015 · Archiv für Experimentelle Pathologie und Pharmakologie
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    ABSTRACT: In the presented study, we attempt to investigate if the sensitization to conditioned place preference (CPP) induced by low doses of morphine was developed in rats which have been previously conditioned with morphine. The experiments were performed in the CPP test. Firstly, it has been demonstrated that administration of ineffective dose of morphine on the 9th day induces the increase in time spent of rats at a morphine-paired compartment, confirming that sensitization to CPP has been developed in these animals. Secondly, it has been shown that stimulation of A1 receptor significantly inhibits the expression of morphine-induced of sensitization, and blockade of these receptors produces the opposite effect. Finally, it has been indicated that both stimulation and blockade of A1 and/or A2A receptors inhibit the acquisition of sensitization to CPP. The obtained results have strongly supported the significance of adenosinergic system in both expression and acquisition of studied sensitization. These results seem to be important for the identification of connections in the central nervous system which can help finding new strategies to attenuate rewarding action of morphine.
    No preview · Article · Dec 2015 · Archiv für Experimentelle Pathologie und Pharmakologie
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    ABSTRACT: Imbalanced matrix metalloproteinase (MMP) activity promotes cardiovascular alterations that are attenuated by statins. These drugs exert pleiotropic effects independent of cholesterol concentrations, including upregulation of nitric oxide (NO) formation and MMP downregulation. However, statins also increase tissue concentrations of nitrites, which activate new signaling pathways independent of NO. We examined whether atorvastatin attenuates MMP-9 production by human umbilical vein endothelial cells (HUVEC) stimulated with phorbol 12-myristate 13-acetate (PMA) by mechanisms possibly involving increased nitrite, and whether this effect results of NO formation. We also examined whether such an effect is improved by sildenafil, an inhibitor of phosphodiesterase-5 which potentiates NO-induced increases in cyclic GMP. MMP activity and nitrite concentrations were measured by gelatin zymography and ozone-based reductive chemiluminescence, respectively, in the conditioned medium of HUVECs incubated for 24 h with these drugs. Phospho-NFκB p65 concentrations were measured in cell lysate to assess NFκB activation. Atorvastatin attenuated PMA-induced MMP-9 gelatinolytic activity by mechanisms not involving NO, although it increased nitrite concentrations, whereas sildenafil had no effects. Combining both drugs showed no improved responses compared to atorvastatin alone. While sodium nitrite attenuated MMP-9 production by HUVECs, adding hemoglobin (NO scavenger) did not affect the responses to nitrite. Neither atorvastatin nor nitrite inhibited PMA-induced increases in phospho-NFκB p65 concentrations. These findings show that sodium nitrite attenuates MMP-9 production by endothelial cells and may explain similar effects exerted by atorvastatin. With both drugs, the inhibitory effects on MMP-9 production are not dependent on NO formation or on inhibition of NFκB activation. Our findings may help to elucidate important new nitrite-mediated mechanisms by which statins affect imbalanced MMP activity in a variety of cardiovascular disease.
    No preview · Article · Nov 2015 · Archiv für Experimentelle Pathologie und Pharmakologie