scholarly journals Anticonvulsant effects of nimodipine alone and combination with phenytoin on MES induced seizures

2018 ◽  
Vol 7 (6) ◽  
pp. 1160
Author(s):  
Raina Jain ◽  
Ashish Jain
Keyword(s):  
Synergistic Effect ◽  
Anticonvulsant Activity ◽  
Hind Limb ◽  
Channel Blockers ◽  
Dependent Manner ◽  
The Novel ◽  
Antiepileptic Activity ◽  
Effective Doses ◽  
Dose Dependent ◽  
Anticonvulsant Effects

Background: To evaluate the anticonvulsant activity of Nimodipine alone and in combination with Phenytoin, in MES induced seizures.Methods: The study was conducted in mice and MES seizure was induced by Techno electroconvulsometer. In first part of study, animals were treated with Nimodipine (20mg/kg i.p. and 40mg/kg i.p.) and Phenytoin (0.5 mg/100g i.p. and 1.0mg/100g i.p.), MES was induced and durations of various phases were noted. Duration of Tonic hind limb extension (THLE) was taken as index for antiepileptic activity. In second part, the animals were treated with combination of sub effective doses of Nimodipine (20mg/kg i.p.) and Phenytoin (0.5mg/100g i.p.), MES was induced and durations of various phases were noted.Results: Nimodipine produced significant antiepileptic activity, in dose dependent manner. Phenytoin produced significant antiepileptic effect in dose of 1.0mg/100g but failed to produce any such effect in dose of 0.5mg/100g, when administered alone. But when sub effective doses.Of Nimodipine and Phenytoin were combined, a synergistic effect was seen.Conclusions: Nimodipine possess significant antiepileptic activity, alone, as well as it potentiates the antiepileptic effect of Phenytoin, suggesting the novel application of already proven safe and efficacious calcium channel blockers.

scholarly journals ANTICONVULSANT EFFECTS OF NIMODIPINE ALONE AND COMBINATION WITH PHENYTOIN ON MES INDUCED SEIZURES

2018 ◽  
Vol 10 (3) ◽  
pp. 44
Author(s):  
Jain Raina ◽  
Jain Ashish
Keyword(s):  
Synergistic Effect ◽  
Calcium Channel Blockers ◽  
Anticonvulsant Activity ◽  
Channel Blockers ◽  
Dependent Manner ◽  
The Novel ◽  
Antiepileptic Activity ◽  
Effective Doses ◽  
Dose Dependent ◽  
Anticonvulsant Effects

Objective: To evaluate the anticonvulsant activity of Nimodipine alone and in combination with Phenytoin, in MES induced seizures.Methods: The study was conducted in mice and MES seizure was induced by Techno electro-convulsometer. In the first part of the study, animals were treated with Nimodipine (20 mg/kg i. p. and 40 mg/kg i. p.) and Phenytoin (0.5 mg/100g i. p. and 1.0 mg/100g i. p.), MES was induced and durations of various phases were noted. Duration of Tonic hindlimb extension (THLE) was taken as an index for antiepileptic activity. In the second part, the animals were treated with a combination of sub effective doses of Nimodipine (20 mg/kg i. p.) and Phenytoin (0.5 mg/100g i. p.), MES was induced and durations of various phases were noted.Results: Nimodipine produced significant antiepileptic activity, in a dose-dependent manner. Phenytoin produced a significant antiepileptic effect in dose of 1.0 mg/100g, but failed to produce any such effect in a dose of 0.5 mg/100g, when administered alone. But when sub-effective doses. Of Nimodipine and Phenytoin were combined, a synergistic effect was seen.Conclusion: Nimodipine posses significant antiepileptic activity, alone, as well as it potentiates the antiepileptic effect of Phenytoin, suggesting the novel application of already proven safe and efficacious calcium channel blockers.

scholarly journals Anticonvulsant Effects of Aerial Parts of Verbena officinalis Extract in Mice: Involvement of Benzodiazepine and Opioid Receptors

2017 ◽  
Vol 22 (4) ◽  
pp. 632-636 ◽  
Author(s):  
Amir Rashidian ◽  
Fatemeh Kazemi ◽  
Saeed Mehrzadi ◽  
Ahmad Reza Dehpour ◽  
Shahram Ejtemai Mehr ◽  
...  
Keyword(s):  
Anticonvulsant Activity ◽  
Hind Limb ◽  
Ethanolic Extract ◽  
Maximal Electroshock ◽  
Dependent Manner ◽  
Reference Drug ◽  
Mes Test ◽  
Aerial Parts ◽  
Tonic Extension ◽  
Dose Dependent

To evaluate the anticonvulsant activity of the aerial parts of Verbena officinalis used traditionally by local Iranians for the treatment of convulsion. The anticonvulsant activity of the extract was assessed in pentylenetetrazole (PTZ) and maximal electroshock (MES) induced seizures in mice. Diazepam was used as reference drug. In addition, for investigating the mechanism of V officinalis in PTZ model, flumazenil and naloxone were injected before V officinalis. The extract showed no toxicity and significantly increased the period taken before the onset and decreased the duration of the seizures induced by PTZ. In the MES test, V officinalis displayed significant reduction in hind limb tonic extension duration in a dose-dependent manner. The results propose that V officinalis ethanolic extract has anticonvulsant activity against seizure. It seems that these effects may be related to potentiating of GABAergic system. Moreover, this study supports the use of this plant by local Iranians in order to treat convulsion.

p-Nitrophenylphosphatase Activity Catalyzed by Plasma Membrane (Ca2++Mg2+)ATPase: Correlation with Structural Changes Modulated by Glycerol and Ca2+

2001 ◽  
Vol 21 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Gutemberg G. Alves ◽  
Luis Maurício T. R. Lima ◽  
Maely P. Fávero-Retto ◽  
Adriana P. Lemos ◽  
Carlos E. Peres-Sampaio ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Synergistic Effect ◽  
Phosphatase Activity ◽  
Structural Changes ◽  
Center Of Mass ◽  
Binding Domain ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Substrate Binding Domain

The plasma membrane (Ca2++Mg2+)ATPase hydrolyzes pseudo-substrates such as p-nitrophenylphosphate. Except when calmodulin is present, Ca2+ ions inhibit the p-nitrophenylphosphatase activity. In this report it is shown that, in the presence of glycerol, Ca2+ strongly stimulates phosphatase activity in a dose-dependent manner. The glycerol- and Ca2+-induced increase in activity is correlated with modifications in the spectral center of mass (average emission wavenumber) of the intrinsic fluorescence of the enzyme. It is concluded that the synergistic effect of glycerol and Ca2+ is related to opposite long-term hydration effects on the substrate binding domain and the Ca2+ binding domain.

scholarly journals Antinociceptive Interaction and Pharmacokinetics of the Combination Treatments of Methyleugenol Plus Diclofenac or Ketorolac

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5106
Author(s):  
Héctor Isaac Rocha-González ◽  
María Elena Sánchez-Mendoza ◽  
Leticia Cruz-Antonio ◽  
Francisco Javier Flores-Murrieta ◽  
Xochilt Itzel Cornelio-Huerta ◽  
...  
Keyword(s):  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Dependent Manner ◽  
Analgesic Drugs ◽  
Isobolographic Analysis ◽  
Combination Treatments ◽  
Significant Difference ◽  
Effective Doses ◽  
Inflammatory Drugs ◽  
Dose Dependent

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the main types of drugs used to treat pain, they have several adverse effects, and such effects can be reduced by combining two analgesic drugs. The aim of this study was to evaluate the nociceptive activity of methyleugenol combined with either diclofenac or ketorolac, and determine certain parameters of pharmacokinetics. For the isobolographic analysis, the experimental effective dose 30 (ED30) was calculated for the drugs applied individually. With these effective doses, the peak plasma concentration (Cmax) was found and the other parameters of pharmacokinetics were established. Methyleugenol plus diclofenac and methyleugenol plus ketorolac decreased licking behavior in a dose-dependent manner in phase II, with an efficacy of 32.9 ± 9.3 and 39.8 ± 9.6%, respectively. According to the isobolographic analysis, the experimental and theoretical ED30 values were similar for methyleugenol plus diclofenac, suggesting an additive effect, but significantly different for methyleugenol plus ketorolac (3.6 ± 0.5 vs. 7.7 ± 0.6 mg/kg, respectively), indicating a probable synergistic interaction. Regarding pharmacokinetics, the only parameter showing a significant difference was Cmax for the methyleugenol plus diclofenac combination. Even with this difference, the combinations studied may be advantageous for treating inflammatory pain, especially for the combination methyleugenol plus ketorolac.

Rapamycin inhibits the growth of cholangiocarcinoma cells in vitro

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15153-15153 ◽  
Author(s):  
T. Sawada ◽  
T. Okada ◽  
K. Kubota
Keyword(s):  
Synergistic Effect ◽  
Cell Lines ◽  
Mtt Assay ◽  
Mrna Level ◽  
Dependent Manner ◽  
In Vitro Methods ◽  
Proliferative Effect ◽  
Cholangiocarcinoma Cell ◽  
Dose Dependent

15153 Background: In the present study, anti-neoplastic effect of rapamycin against cholangiocarcinoma was studied in vitro. Methods: Expression of mTOR in 4 cholangiocarcinoma cell lines, TFK1, HuCCT1, NOZW, and OZ was evaluated by real-time PCR. Then, the four cholangiocarcinoma cell lines were cultured with rapamycin (0, 25, 50, 100, 200 nM), gemcitabine (0, 0.5, 1, 2 μM), or both, and anti-proliferative effect was evaluated by MTT assay. Results: All the four cholangiocarcinoma cell lines expressed endogenous mTOR- mRNA. Level of expression was the highest in HuCCT1 (65.8), and the lowest in TFK1 (17.6). Then, rapamycin significantly inhibited the growth of all the four cholangiocarcinoma cell lines, in dose-dependent manner. Gemcitabine inhibited the growth of NOZW (48.4%) and HuCCT1 (48.9%), but less efficiently in TFK1 (5.9%) and OZ (27.4%). Furthermore, synergistic anti-proliferative effect of rapamycin and gemcitabine was observed in TFK1 (39.1%), NOZW (38.9%), and OZ (47.1%), not in HuCCT1 (18.9%). Conclusion: Rapamycin effectively inhibited the growth of the cholangiocarcinoma cell lines, and synergistic effect with gemcitabine was observed in three of the four cell lines. No significant financial relationships to disclose.

scholarly journals Nesfatin-1 Suppresses Cardiac L-type Ca2+ Channels Through Melanocortin Type 4 Receptor and the Novel Protein Kinase C Theta Isoform Pathway

2015 ◽  
Vol 36 (2) ◽  
pp. 555-568 ◽  
Author(s):  
Jiaoqian Ying ◽  
Yuan Zhang ◽  
Shan Gong ◽  
Zhigang Chang ◽  
Xiaofeng Zhou ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ventricular Myocytes ◽  
Dependent Manner ◽  
The Novel ◽  
Inotropic Effects ◽  
Kinase C ◽  
Melanocortin 4 Receptor ◽  
Dose Dependent ◽  
Ca2 Channels

Background/Aims: Nesfatin-1 (NF-1), an anorexic nucleobindin-2 (NUCB2)-derived hypothalamic peptide, acts as a peripheral cardiac modulator and it can induce negative inotropic effects. However, the mechanisms underlying these effects in cardiomyocytes remain unclear. Methods: Using patch clamp, protein kinase assays, and western blot analysis, we studied the effect of NF-1 on L-type Ca2+ currents (ICa,L) and to explore the regulatory mechanisms of this effect in adult ventricular myocytes. Results: NF-1 reversibly decreased ICa,L in a dose-dependent manner. This effect was mediated by melanocortin 4 receptor (MC4-R) and was associated with a hyperpolarizing shift in the voltage-dependence of inactivation. Dialysis of cells with GDP-β-S or anti-Gβ antibody as well as pertussis toxin pretreatment abolished the inhibitory effects of NF-1 on ICa,L. Protein kinase C (PKC) antagonists abolished NF-1-induced responses, whereas inhibition of PKA activity or intracellular application of the fast Ca2+-chelator BAPTA elicited no such effects. Application of NF-1 increased membrane abundance of PKC theta isoform (PKCθ), and PKCθ inhibition abolished the decrease in ICa,L induced by NF-1. Conclusion: These data suggest that NF-1 suppresses L-type Ca2+ channels via the MC4-R that couples sequentially to the βγ subunits of Gi/o-protein and the novel PKCθ isoform in adult ventricular myocytes.

Swelling-activated efflux of taurine and other organic osmolytes in endothelial cells

1997 ◽  
Vol 273 (1) ◽  
pp. C214-C222 ◽  
Author(s):  
V. G. Manolopoulos ◽  
T. Voets ◽  
P. E. Declercq ◽  
G. Droogmans ◽  
B. Nilius
Keyword(s):  
Endothelial Cells ◽  
Anion Channel ◽  
Disulfonic Acid ◽  
Channel Blockers ◽  
Organic Osmolytes ◽  
Dependent Manner ◽  
Anion Channels ◽  
Whole Cell Patch Clamp ◽  
Osmolyte Efflux ◽  
Dose Dependent

We used a combined biochemical, pharmacological, and electrophysiological approach to study the effects of hyposmotic swelling on organic osmolyte efflux in endothelial cells (EC). In [3H]taurine-loaded monolayers of calf pulmonary artery EC (CPAEC), hyposmolality activated time- and dose-dependent effluxes of [3H]taurine. Swelling-activated [3H]taurine efflux (Jtau swell)in CPAEC was inhibited by the anion channel blockers tamoxifen, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), fenamates, and also quinine (in a pH-dependent manner), ATP, and the phospholipase A2 inhibitor 4-bromophenacyl bromide. In contrast, Jtau swell was partly or totally insensitive to bumetanide, forskolin, phorbol 12-myristate 13-acetate, and staurosporine. Swelling also activated myo-[3H]inositol efflux that was blocked by tamoxifen, NPPB, DIDS, and niflumic acid. Moreover, the cellular content of taurine and other amino acids was significantly reduced in osmotically activated CPAEC. Finally, in whole cell patch-clamp experiments, taurine, glycine, aspartate, and glutamate exhibited significant permeability for swelling-activated anion channels. In conclusion, hyposmotic swelling activates efflux of taurine and other organic osmolytes in EC. In addition, our results suggest that anion channels may provide a pathway for swelling-activated efflux of organic osmolytes in EC.

The novel antiviral properties of brassicasterol against human adenovirus

2021 ◽  
Author(s):  
Peifeng Yu ◽  
Dan Lou ◽  
Lifeng Qi ◽  
Zewei Chen
Keyword(s):  
Dna Replication ◽  
Epithelial Cells ◽  
Viral Entry ◽  
Human Adenovirus ◽  
Airway Epithelial Cells ◽  
Dependent Manner ◽  
The Novel ◽  
Airway Epithelial ◽  
Infected Cells ◽  
Dose Dependent

Aim: To investigate whether brassicasterol has inhibitory effects against adenovirus (AdV). Materials and methods: The antiviral effects of brassicasterol against AdV 3 and 7 were tested in human airway epithelial cells. Brassicasterol cytotoxicity was assessed by WST-1 assay. AdV DNA was quantified by qPCR. Results: Brassicasterol inhibited AdV 3 and 7 infection of airway epithelial cells in a dose-dependent manner. Similarly, brassicasterol also inhibited AdV 3 and 7 production in infected cells. No apparent cytotoxicity of brassicasterol was detected. Further study showed that brassicasterol inhibited AdV DNA replication, but had no impact on viral entry of cells and viral genome import to nucleus. Conclusion: Brassicasterol exerts anti-AdV effects probably through the inhibition of viral DNA replication.

Effect of Na-channel blockers and lumen Ca on K secretion by rat renal distal tubule

1991 ◽  
Vol 260 (3) ◽  
pp. F459-F465 ◽  
Author(s):  
M. D. Okusa ◽  
H. Velazquez ◽  
F. S. Wright
Keyword(s):  
Extracellular Fluid ◽  
Distal Tubule ◽  
Na Channel ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Channel Blocking ◽  
K Secretion ◽  
Ca Ions ◽  
Transepithelial Voltage ◽  
Dose Dependent

In previous studies the effectiveness of amiloride (AML) in reducing K secretion has been variable. Based on studies by Cuthbert and Wong (Mol. Pharmacol. 8: 222-229, 1972) in which the Na-channel-blocking action of AML in frog skin was found to require the availability of Ca ions in extracellular fluid, we postulated that the ability of AML and its analogue, benzamil (BZA), to inhibit distal tubule K secretion depends on the presence of Ca in luminal fluid. We found that addition of Ca to a perfusion solution containing 50 microM BZA did reduce K secretion more than BZA alone. Maximal inhibition was observed with 2.5 mM free ionic Ca. Graded increases in luminal Ca in presence of AML or BZA reduced K transport in a dose-dependent manner. The decrease in K secretion with increasing luminal Ca was paralleled by a decrease in transepithelial voltage. These results support our hypothesis that the effectiveness of Na-channel blockers to reduce K secretion by the rat distal tubule depends on presence of luminal Ca and suggest an interaction between luminal Ca and Na-channel blockers on the Na channel.

Isoflurane-induced Dilation of Porcine Coronary Microvessels Is Endothelium Dependent and Inhibited by Glibenclamide

2002 ◽  
Vol 96 (6) ◽  
pp. 1465-1471 ◽  
Author(s):  
A. Kurt Gamperl ◽  
Travis W. Hein ◽  
Lih Kuo ◽  
Brian A. Cason
Keyword(s):  
Potassium Channel ◽  
Sodium Nitroprusside ◽  
Adenosine Triphosphate ◽  
Channel Blocker ◽  
Minimum Alveolar Concentration ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Presence And Absence ◽  
Dose Dependent

Background Isoflurane has been reported to cause dose-dependent constriction in isolated coronary microvessels. However, these results are inconsistent with data from in situ and in vivo heart preparations which show that isoflurane dilates the coronary vasculature. To clarify the direct effects of isoflurane on coronary tone, we measured the response of isolated porcine resistance arterioles (ID, 75 +/- 4.0 microm; range, 41-108 microm) to isoflurane in the presence and absence of adenosine triphosphate-sensitive and Ca2+-activated potassium channel blockers and also after endothelial removal. Methods Subepicardial arterioles were isolated, cannulated, and pressurized to 45 mmHg without flow in a 37 degrees C vessel chamber filled with MOPS buffer (pH = 7.4). After all vessels developed spontaneous (intrinsic) tone, dose-dependent (0.17-0.84 mm; approximately 0.5-2.5 minimum alveolar concentration) isoflurane-mediated effects on vessel ID were studied in the presence and absence of extraluminal glibenclamide (1 microm; an adenosine triphosphate-sensitive channel blocker) or iberiotoxin (100 nm; a Ca2+-activated potassium channel blocker) or before and after endothelial denudation using the nonionic detergent CHAPS (0.4%). Vessel ID was measured using an inverted microscope and videomicrometer, and vasomotor responses were analyzed by normalizing changes in arteriole ID to the dilation observed after exposure to 10-4 m sodium nitroprusside, which causes maximal dilation. Results Isoflurane caused dose-dependent dilation of all coronary arterioles. This vasodilation was 6.0 +/- 0.7 microm at an isoflurane concentration of 0.16 mm (approximately 0.5 minimum alveolar concentration) and 25.3 +/- 2.1 microm at 0.75 mm (approximately 2.5 minimum alveolar concentration). These values represent 18.1 +/- 1.7% and 74.1 +/- 3.3%, respectively, of that observed with 10-4 sodium nitroprusside (34 +/- 3 microm). Glibenclamide, but not iberiotoxin, exposure affected arteriolar dilation in response to isoflurane. Glibenclamide caused a downward displacement of the isoflurane dose-response curve, reducing isoflurane-mediated dilation by an average of 36%. Denuded arterioles showed a marked (approximately 70%) reduction in their ability to dilate in response to isoflurane. Conclusions The authors conclude that isoflurane dilates coronary resistance arterioles in a dose-dependent manner, and that this dilation is partially mediated by adenosine triphosphate-sensitive channels and is highly dependent on the presence of a functioning endothelium.

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