Effects Of Verapamil Research Articles

Effects of combined drug treatments on Plasmodium falciparum: In vitro assays with doxycycline, ivermectin and efflux pump inhibitors.

There is great concern regarding the rapid emergence and spread of drug-resistance in Plasmodium falciparum, the parasite responsible for the most severe form of human malaria. Parasite populations resistant to some or all the currently available antimalarial treatments are present in different world regions. Considering the need for novel and integrated approaches to control malaria, combinations of drugs were tested on P. falciparum. The primary focus was on doxycycline, an antibiotic that specifically targets the apicoplast of the parasite. In combination with doxycycline, three different drugs known to inhibit efflux pumps (verapamil, elacridar and ivermectin) were tested, with the assumption that they could increase the intracellular concentration of the antibiotic and consequently its efficacy against P. falciparum. We emphasize that elacridar is a third-generation ABC transporters inhibitor, never tested before on malaria parasites. In vitro experiments were performed on asexual stages of two strains of P. falciparum, chloroquine-sensitive (D10) and chloroquine-resistant (W2). Incubation times on asynchronous or synchronous cultures were 72h or 96h, respectively. The antiplasmodial effect (i.e. the IC50) was determined by measuring the activity of the parasite lactate dehydrogenase, while the interaction between drugs was determined through combination index (CI) analyses. Elacridar achieved an IC50 concentration comparable to that of ivermectin, approx. 10-fold lower than that of verapamil, the other tested ABC transporter inhibitor. CI results showed synergistic effect of verapamil plus doxycycline, which is coherent with the starting hypothesis, i.e. that ABC transporters represent potential targets, worth of further investigations, towards the development of companion molecules useful to enhance the efficacy of antimalarial drugs. At the same time, the observed antagonistic effect of doxycycline in combination with ivermectin or elacridar highlighted the importance of drug testing, to avoid the de-facto generation of a sub-dosage, a condition that facilitates the development of drug resistance.

Mechano-Pharmacological Testing of L-Type Ca2+ Channel Modulators via Human Vascular Celldrum Model

This study aimed to establish a precise and well-defined working model, assessing pharmaceutical effects on vascular smooth muscle cell monolayer in-vitro. It describes various analysis techniques to determine the most suitable to measure the biomechanical impact of vasoactive agents by using CellDrum technology. The so-called CellDrum technology was applied to analyse the biomechanical properties of confluent human aorta muscle cells (haSMC) in monolayer. The cell generated tensions deviations in the range of a few N/m² are evaluated by the CellDrum technology. This study focuses on the dilative and contractive effects of L-type Ca2+ channel agonists and antagonists, respectively. We analyzed the effects of Bay K8644, nifedipine and verapamil. Three different measurement modes were developed and applied to determine the most appropriate analysis technique for the study purpose. These three operation modes are called, particular time mode" (PTM), "long term mode" (LTM) and "real-time mode" (RTM). It was possible to quantify the biomechanical response of haSMCs to the addition of vasoactive agents using CellDrum technology. Due to the supplementation of 100nM Bay K8644, the tension increased approximately 10.6% from initial tension maximum, whereas, the treatment with nifedipine and verapamil caused a significant decrease in cellular tension: 10nM nifedipine decreased the biomechanical stress around 6,5% and 50nM verapamil by 2,8%, compared to the initial tension maximum. Additionally, all tested measurement modes provide similar results while focusing on different analysis parameters. The CellDrum technology allows highly sensitive biomechanical stress measurements of cultured haSMC monolayers. The mechanical stress responses evoked by the application of vasoactive calcium channel modulators were quantified functionally (N/m²). All tested operation modes resulted in equal findings, whereas each mode features operation-related data analysis.

Effect of tetracycline and verapamil on reproductive hormones and liver enzymes of female albino rats

Effect of tetracycline and verapamil on reproductive hormones and liver enzymes of female albino rats

Nicardipine Inhibits Priming of the NLRP3 Inflammasome via Suppressing LPS-Induced TLR4 Expression.

The Nod-like receptor protein 3 (NLRP3) inflammasome is a multi-protein complex composed of NLRP3, pro-caspase-1, and apoptosis-associated speck-like protein that contains a caspase recruitment domain (ASC). After NLRP3 priming by lipopolysaccharide (LPS), the ligand of toll-like receptor 4 (TLR4), activation of the NLRP3 inflammasome triggers caspase-1 maturation, leading to pyroptosis and release of interleukin-1beta (IL-1beta). Expression of TLR4 modulates LPS-triggered inflammatory cascades as well as the NLRP3 signaling. L-type calcium channel antagonists are widely used as anti-hypertensive drugs and also exert anti-inflammatory effects through inhibiting release of cytokines including IL-1beta. However, few studies reveal effects of L-type calcium channel antagonists on the NLRP3 inflammasome. In this study, we investigated the effects of nicardipine and verapamil, both L-type calcium channel antagonists, on the NLRP3 inflammasome using differentiated THP-1 cells. Pyroptosis or levels of IL-1beta and caspase-1 were assayed by flow cytometry or enzyme-linked immunosorbent assay, respectively. ASC oligomerization was assayed by immunofluorescence microscopy. Expression of NLRP3 or TLR4 was assayed by polymerase chain reaction and immunoblotting. Nuclear factor-kappaB (NF-kappaB) pathway was also studied. Our results showed that pyroptosis and IL-1beta release were attenuated by nicardipine, but not verapamil. Nicardipine also mitigated caspase-1 activation, inhibited ASC oligomerization, and reduced NLRP3 expression. Furthermore, nicardipine downregulated phosphorylation or nuclear translocation of NF-kappaB p65, consistent with the inhibitory effect of nicardipine on LPS-induced TLR4 expression. In conclusion, nicardipine exerted anti-inflammatory effects through inhibiting NLRP3 inflammasome pathway. Nicardipine may mitigate NLRP3 priming via inhibiting NF-kappaB activation, mediated by suppressing LPS-induced TLR4 expression.

Effect of tetracycline and verapamil on reproductive hormones and liver enzymes of female albino rats

Effect of tetracycline and verapamil on reproductive hormones and liver enzymes of female albino rats

Verapamil extends lifespan in Caenorhabditis elegans by inhibiting calcineurin activity and promoting autophagy.

Previous evidence has revealed that increase in intracellular levels of calcium promotes cellular senescence. However, whether calcium channel blockers (CCBs) can slow aging and extend lifespan is still unknown. In this study, we showed that verapamil, an L-type calcium channel blocker, extended the Caenorhabditis elegans (C. elegans) lifespan and delayed senescence in human lung fibroblasts. Verapamil treatment also improved healthspan in C. elegans as reflected by several age-related physiological parameters, including locomotion, thrashing, age-associated vulval integrity, and osmotic stress resistance. We also found that verapamil acted on the α1 subunit of an L-type calcium channel in C. elegans. Moreover, verapamil extended worm lifespan by inhibiting calcineurin activity. Furthermore, verapamil significantly promoted autophagy as reflected by the expression levels of LGG-1/LC3 and the mRNA levels of autophagy-related genes. In addition, verapamil could not further induce autophagy when tax-6, calcineurin gene, was knocked down, indicating that verapamil-induced lifespan extension is mediated via promoting autophagy processes downstream of calcineurin. In summary, our study provided mechanistic insights into the anti-aging effect of verapamil in C. elegans.

Changes in Ca2+ release in human red blood cells under pulsed magnetic field

Since Ca2+ is related to a highly versatile intracellular signal to regulate many different cellular processes, the role of Ca2+ and its concentration in red blood cells (RBCs) are very important. Accordingly, in this study, we have elucidated the relationship between pulsed magnetic field (PMF) and intracellular Ca2+ level to understand how PMF affects oxidative stressed RBCs. In addition, the effect of verapamil on RBCs in Ca2+ level, compared to the effect of PMF was investigated because verapamil, as a reducing agent, blocks Ca2+ influx into RBCs. Tert-butyl hydroperoxide (tBHP) was used to induce oxidative stress in RBCs with various concentrations of 0.1 to 400 mM. Our PMF stimulator has the maximum intensity of 0.27 T at a transition time of 102 μs with pulse intervals of 1 Hz. Our result showed that Ca2+ level is remarkably decreased in RBCs treated verapamil, RBCs exposed to PMF after tBHP(0.1 mM) treatment, and RBCs treated tBHP(0.1 mM) after PMF exposure, respectively. This means that PMF not only reduces Ca2+ level of inner RBC effectively but also blocks inhibiting Ca2+ pump ATPase activity. Also it seems that PMF appears to act similar to reducing agent. For hemolysis change in oxidative stressed RBCs with or without PMF, using western blot and gel analysis, it is observed that hemolysis declines in control RBCs and tBHP(0.1 mM)-treated RBCs exposed to PMF, and in verapamil treated sample. The RBC deformability (RBCD) was also improved after PMF exposure. Therefore, the results of the present study support that PMF gives RBCs positive effect consistently in Ca2+ level and plays a role in preventing RBC hemolysis from oxidative stress and improving RBCD. In conclusion, our study suggests a possibility to use PMF as a new modality in improving circulatory regulation in hemodynamic derangements in disease. We need to optimize PMF intensity and stimulated duration for clinical use.

99mTc-MIBI uptake as a marker of mitochondrial membrane potential in cancer cells and effects of MDR1 and verapamil.

We investigated the relation of 99mTc-MIBI uptake to mitochondrial membrane potential (MMP) in cancer cell lines and patient-derived tumor cells (PDCs). In T47D and HT29 cells with low MDR1 expression, FCCP dose-dependently reduced MMP and 99mTc-MIBI accumulation in similar patterns with nearly perfect linear relationships. T47D and HT29 cells with high MDR1 expression had low 99mTc-MIBI accumulation that was minimally affected by FCCP dose. In these cells, verapamil markedly increased 99mTc-MIBI accumulation to magnitudes that were excessive compared to MMP increase. Decreased plasma membrane potential by verapamil and its recovery by FCCP suggested that enhanced 99mTc-MIBI transport through modified plasma membranes contributed to the excess accumulation. Evaluation of three different colon cancer PDCs with low to modest MDR1 expression verified that FCCP significantly suppressed MMP and similarly reduced 99mTc-MIBI accumulation. Verapamil partially recovered both MMP and 99mTc-MIBI accumulation that was lowered by FCCP. Importantly, a high linear correlation was found (r = 0.865) between 99mTc-MIBI accumulation and MMP in these cells. These findings indicate that low baseline 99mTc-MIBI uptake that is markedly increased by verapamil represents cancer cells with high levels of MDR1 expression. However, in cancer cells with low or modest levels of MDR1 expression that do not markedly increase 99mTc-MIBI uptake by verapamil, the magnitude of uptake is largely dependent on cellular MMP.

Electrophysiological Examination of the Effects of Classical Pharmacological Agent Verapamil in Plant Based Model System

Homologs of human two pore channels (TPC) were documented in plants thus the examination of the effects of medicines against TPC-related diseases could be performed in plant model systems. Examination of electrical signalling properties - generation of Action Potentials (AP) - in Characeaen macroalgae Nitellopsis obtusa is an established method offering insights into effects of ion channel modulators in vivo. Standardized current clamp and voltage clamp approaches have been used for this purpose for decades. Verapamil is a well-known L-type Ca2+ channel blocker, also it was demonstrated to inhibit Kv channels in a variety of tissues and cells. Investigation of changes in ion currents during AP generation after verapamil treatment was carried out by the application of the C-C, V-C and patch clamp techniques in Nitellopsis obtusa model system. High discretization frequency allowed high temporal resolution analysis of real-time processes such as changes in excitation threshold, AP amplitude and velocity of repolarization phase along with activation/inactivation dynamics of ion channels. These parameters reflected modulation of activity of ion channels involved in AP generation. The effect of verapamil was found to be concentration dependent and manifested as a depolarization of membrane resting potential and excitation threshold, also as an increase of AP duration as well as a prolongation of inactivation times of transient currents during excitation. Our investigation demonstrate direct and rapid effect of verapamil on electrical signalling in plants on single cell level. The research was funded by DAINA – Polish-Lithuanian joint project S-LL-18-1.

Comparative Study of Protective Effect of Cimetidine and Verapamil on Paracetamol-Induced Hepatotoxicity in Mice.

Paracetamol, chemically known as acetaminophen, if taken in higher doses has hepatotoxic potential. Cimetidine by inhibiting the cytochromal enzymes and reducing the production of the toxic metabolite can reduce the hepatotoxic potential while Verapamil can act as a hepatoprotective by maintaining calcium homeostasis. The present study was conducted to study the hepatoprotective activity of Cimetidine and Verapamil against the toxicity induced by paracetamol. In addition to the group receiving only distilled water or 300 mg/kg paracetamol additional groups were added treated with 150 mg/kg Cimetidine and Verapamil alone or both. The Liver function tests and histopathology revealed hepatotoxicity in the group receiving paracetamol (PCM) while normal parameters were observed in the groups receiving Cimetidine and Verapamil. Our results strongly suggested that Cimetidine and Verapamil possess hepatoprotective potential against paracetamol induced hepatotoxicity.

Effect of verapamil on the pharmacokinetics of hydroxycamptothecin and its potential mechanism

Context Hydroxycamptothecin (HCPT) has antitumor activity in various cancers, but its poor bioavailability and efflux limit its clinical application. Verapamil has been demonstrated to improve the bioavailability of many drugs. However, the effect of verapamil on the pharmacokinetics of HCPT was not clear. Objective The effect of verapamil on the pharmacokinetics of HCPT was investigated to clarify the drug–drug interaction between HCPT and verapamil. Materials and methods The pharmacokinetic profiles of oral administration of HCPT (50 mg/kg) in two group of Sprague–Dawley rats (six rats each), with pre-treatment of verapamil (10 mg/kg/day) for 7 days were investigated, with the group without verapamil pre-treatment as control. Additionally, the metabolic stability and transport of HCPT in the presence or absence of verapamil were also investigated with the employment of the rat liver microsomes and Caco-2 cell transwell model. Results Verapamil significantly increased the peak plasma concentration (from 91.97 ± 11.30 to 125.30 ± 13.50 ng/mL), and decrease the oral clearance (from 63.85 ± 10.79 to 32.95 ± 6.17 L/h/kg). The intrinsic clearance rate was also significantly decreased (from 39.49 ± 0.42 to 28.64 ± 0.30 μL/min/mg protein) by the preincubation of verapamil. The results of Caco-2 cell transwell experiments showed the efflux of HCPT was inhibited by verapamil, as the efflux ratio decreased from 1.82 to 1.21. Discussion and conclusions The system exposure of HCPT was increased by verapamil. Verapamil may exert this effect through inhibiting the activity of CYP3A4 or P-gp, which are related to the metabolism and transport of HCPT.

Antifungal and anti-biofilm effect of the calcium channel blocker verapamil on non-albicans Candida species.

Candida is a human fungal pathogen that causes a wide range of diseases. Candida albicans is the main etiologic agent in these diseases; however, infections can be caused by non-albicans Candida species. Virulence factors such as biofilm production, which protect the fungus from host immunity and anti-fungal drugs, are important for the infection. Therefore, available antifungal drugs for candidiasis treatment are limited and the investigation of new and effective drugs is needed. Verapamil is a calcium channel blocker with an inhibitory effect on hyphae development, adhesion, and colonization of C. albicans. In this study, we investigated the effect of verapamil on cell viability and its antifungal and anti-biofilm activity in non-albicans Candida species. Verapamil was not toxic to keratinocyte cells; moreover, C. krusei, C. parapsilosis, and C. glabrata were susceptible to verapamil with a minimal inhibitory concentration (MIC) of 1250 μM; in addition, this drug displayed fungistatic effect at the evaluated concentrations. After treatment with verapamil, reduced viability, biomass, and mitochondrial activity were observed in biofilms of the non-albicans Candida species C. krusei, C. glabrata, and C. parapsilosis. These findings highlight the importance of the study of verapamil as an alternative treatment for infections caused by non-albicans Candida species.

Effect of Vasodilatory Medications on Blood Pressure in Patients Undergoing Transradial Coronary Angiography: A Comparative Study.

Background:In patients undergoing coronary intervention, different vasodilators are used to prevent the radial artery spasm (RAS). To date, no studies investigated the effect of these vasodilators in blood pressure (BP) reduction.Aim:The study aimed to investigate and compare the effect of vasodilatory medications on BP reduction in patients undergoing transradial coronary angiography procedure.Methods:We consecutively included 300 patients undergoing transradial coronary angiography procedures and randomly assigned them into three equal groups to compare the effect of verapamil (2.5 mg), nitroglycerin (200 μg), and combination (verapamil 2.5 mg with nitroglycerin 200 (μg) was diluted in 5 ml of normal saline and given through radial sheath. Changes in the BP, heart rate (HR), and other clinical parameters were assessed and presented as standardized mean differences (SMD) with 95% confidence intervals (CIs). ANOVA test was performed to analyze the differences in the BP and other clinical parameters between the three groups.Results:Overall, the mean age of the study population was 53.26 years (standard deviation: 9.27), male patients (84%), with dyslipidemia (62.6%), and diabetes (45%). At baseline, the mean systolic BP (SBP) was 150.91 ± 31.66 mmHg, HR (72.34 ± 12.71 beats/min). After the administration of vasodilators, the combination group reduced SBP significantly (SMD: −33.35 [95% CI]: −40.27–−26.42, P < 0.001). There was a statistically significant difference between groups for the SBP (F [2,296] =3.38, P = 0.035). Verapamil alone showed a significant decrease in the SBP by −27.23 mmHg and diastolic BP by −4.980 mmHg.Conclusion:Intra-arterial administration of verapamil alone showed lower BP reduction compared to the combination of vasodilators. Verapamil could be a safer and effective alternative to prevent RAS with no deleterious effect on BP and HR in patients undergoing transradial coronary angiography.

Сравнение действия верапамила как ингибитора АВС-транспортёров при различных путях поступления в организм рыжего таракана Blattella germanica (Blattodea: Ectobiidae)

Сравнение действия верапамила как ингибитора АВС-транспортёров при различных путях поступления в организм рыжего таракана Blattella germanica (Blattodea: Ectobiidae)

Micro-patterned SU-8 cantilever integrated with metal electrode for enhanced electromechanical stimulation of cardiac cells

Over the past few years, cardiac tissue engineering has undergone tremendous progress. Various in vitro methods have been developed to improve the accuracy in the result of drug-induced cardiac toxicity screening. Herein, we propose a novel SU-8 cantilever integrated with an electromechanical-stimulator to enhance the maturation of cultured cardiac cells. The simultaneous electromechanical stimulation significantly enhances the contraction force of the cardiomyocytes, thereby increasing cantilever displacement. Fluorescence microscopy analysis was performed to confirm the improved maturation of the cardiomyocytes. After the initial experiments, the contractile behaviors of the cultured cardiomyocytes were investigated by measuring the mechanical deformation of the SU-8 cantilever. Finally, the proposed electromechanical-stimulator-integrated SU-8 cantilever was used to evaluate the adverse effects of different cardiac vascular drugs, i.e., verapamil, lidocaine, and isoproterenol, on the cultured cardiomyocytes. The physiology of the cardiac-drug-treated cardiomyocytes was examined with and without electrical stimulation of the cardiomyocytes. The experimental results indicate that the proposed cantilever platform can be used as a predictive assay system for preliminary cardiac drug toxicity screening applications.

Verapamil and collagenase differentially affect collagen metabolism in experimental model of Peyronie's disease

ObjectivesPeyronie's disease (PD) is accompanied by remodelling of connective tissue into fibrotic plaque. Treatment of the inflammatory and fibrotic phases of the disease is not established. The aim of the study was to evaluate the effect of verapamil (VER) and bacterial collagenase (COLL) on collagen metabolism and cell migration in fibroblasts with experimental wound healing and inflammation as an in vitro model of PD. Materials and methodsIn vitro model of PD was designed using experimental model of inflammation induced by Interleukin-1 (IL-1) in cultured fibroblasts and mechanical damage of the cells. Cell viability, cell proliferation, collagen biosynthesis, prolidase activity and cell migration were studied in both models of the cells treated with VER and COLL. ResultsVER decreased cell viability, DNA and collagen biosynthesis and increased prolidase activity in control fibroblast, while in “wounded” fibroblasts it significantly decreased all the processes. COLL did not affect cell viability and DNA biosynthesis, while inhibited collagen biosynthesis and prolidase activity in both control and “wounded” fibroblasts. In IL-1-treated fibroblasts VER inhibited all studied processes except prolidase activity, while COLL inhibited only collagen biosynthesis and prolidase activity. COLL accelerated cell migration, while VER attenuated the process in fibroblast model of wound healing, compared to control cells. ConclusionVER and COLL attenuate collagen biosynthesis in both fibroblast models. The VER-dependent inhibition of collagen biosynthesis was accompanied by inhibition of DNA biosynthesis at high prolidase activity, while COLL affected this process through inhibition of prolidase activity at high rate of DNA biosynthesis. It shows that anti-fibrotic activity of VER/COLL and anti-inflammatory activity of VER may represent approach to establish standard treatment of PD.

The effects of verapamil and heparin co-administration on sperm parameters and oxidative stress in prevention of testicular torsion/detorsion damage in rats.

In this research, the impacts of combined administration of verapamil and heparin on testicular torsion damage were examined. In this experimental study, 30 sexually mature male Wistar albino rats were divided into five equal groups haphazardly (n=6): Group 1 was the sham group. In group 2, a 2-hr testicular torsion was induced, and thereafter, detorsion was done. Rats in group 3 and group 4 experienced an identical surgical procedure like group 2, but verapamil and heparin were administered in 0.3mg/kg and 800IU/kg doses respectively, and in group 5, a combination of verapamil and heparin were administered. Intraperitoneal drug injection in all treatment groups was done 30min before testicular detorsion. Testicular torsion significantly changed sperm parameters, oxidative stress biomarkers and Cosentino's histological score compared to the sham group (p<.05). All treatment groups reduced testicular damage by decreasing oxidative stress and improving sperm parameters, but heparin and co-administration of verapamil and heparin were significantly better than verapamil injection alone. However, heparin injected groupwas more effective than other treatment groups (p<.05). Overall, an anticoagulant like heparin is more effective than a calcium channel blocker such as verapamil, and it is more likely to reduce testicular torsion injuries.

Pathophysiology of and therapeutic options for a GABRA1 variant linked to epileptic encephalopathy

We report the identification of a de novo GABRA1 (R214C) variant in a child with epileptic encephalopathy (EE), describe its functional characterization and pathophysiology, and evaluate its potential therapeutic options. The GABRA1 (R214C) variant was identified using whole exome sequencing, and the pathogenic effect of this mutation was investigated by comparing wild-type (WT) α1 and R214C α1 GABAA receptor-expressing HEK cells. GABA-evoked currents in these cells were recorded using whole-cell, outside-out macro-patch and cell-attached single-channel patch-clamp recordings. Changes to surface and total protein expression levels of WT α1 and R214C α1 were quantified using surface biotinylation assay and western blotting, respectively. Finally, potential therapeutic options were explored by determining the effects of modulators, including diazepam, insulin, and verapamil, on channel gating and receptor trafficking of WT and R214C GABAA receptors. We found that the GABRA1 (R214C) variant decreased whole-cell GABA-evoked currents by reducing single channel open time and both surface and total GABAA receptor expression levels. The GABA-evoked currents in R214C GABAA receptors could only be partially restored with benzodiazepine (diazepam) and insulin. However, verapamil treatment for 24 h fully restored the function of R214C mutant receptors, primarily by increasing channel open time. We conclude that the GABRA1 (R214C) variant reduces channel activity and surface expression of mutant receptors, thereby contributing to the pathogenesis of genetic EE. The functional restoration by verapamil suggests that it is a potentially new therapeutic option for patients with the R214C variant and highlights the value of precision medicine in the treatment of genetic EEs.

Verapamil attenuates scopolamine induced cognitive deficits by averting oxidative stress and mitochondrial injury - A potential therapeutic agent for Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial disorder where amyloid beta (Aβ) plaques, Ca2+ dysregulation, excessive oxidative stress, mitochondrial dysfunction and synaptic loss operate synergistically to bring about cholinergic deficits and dementia. New therapeutic interventions are gaining prominence as the morbidity and mortality of AD increases exponentially every year. Treating AD with antihypertensive drugs is thought to be a promising intervention; however, its mechanism of action of ameliorating AD needs further investigation. In this context, the present study explores the protective effect of verapamil, an antihypertensive agent of Ca2+ channel blocker (CCB) class against scopolamine-induced in vitro neurotoxicity and in vivo cognitive impairment. Supplementation of verapamil was found to attenuate oxidative stress by preventing mitochondrial injury, and augment the expression of genes involved in the cholinergic function (mACR1), synaptic plasticity (GAP43, SYP) and Ca2+-dependent memory-related genes (CREB1, CREBBP, BDNF). Further, verapamil treatment in mice attenuated the cognitive and behavioural deficits induced by scopolamine as measured by the elevated plus maze and passive avoidance test (P < 0.05). Thus, the present study demonstrates the neuroprotective effect of verapamil against the pathogenesis of AD such as oxidative stress, mitochondrial dysfunction and cognitive decline. These observations emphasize the importance of ‛Ca2+ dysregulation' and ‛mitochondrial dysfunction' theories in AD and recommends the supplementation of compounds that regulate Ca2+ homeostasis and mitochondrial function in susceptible AD individuals.

Antinociceptive and anti-inflammatory effects of N-acetylcysteine and verapamil in Wistar rats.

BackgroundAntinociceptive anti-inflammatory drugs have many adverse effects. The goal of this investigation is to study the probable anti-inflammatory and analgesic effects of verapamil and N-acetylcysteine (NAC) in experimental rats.MethodsAdult male Wistar rats were randomly divided into 4 groups in the antinociceptive study, each containing 6 rats; the normal control group, which received saline (1 mL/kg); the diclofenac group, which received diclofenac sodium (5 mg/kg); the NAC group, which received NAC (125 mg/kg); and the verapamil group, which received verapamil (8 mg/kg). In the anti-inflammatory study, 5 groups were used, the 4 previous groups with the addition of an edema control group, received saline and were subjected to formalin test. Hot plate latency time was recorded for antinociceptive evaluation. Paw edema thickness and biochemical parameters were recorded for anti-inflammatory evaluation.ResultsAdministration of NAC showed significant prolongation of hot plate latency time at 1 hour when compared to the control group while verapamil showed a significant prolongation of hot plate latency time at 1 and 2 hours when compared to the control group and NAC group values. Administration of NAC and verapamil significantly decreased paw edema thickness at 2, 4, and 8 hours when compared to edema control values. Regarding biochemical markers, NAC and verapamil significantly decreased serum nitric oxide synthase, C-reactive protein, and cyclooxygenase-2 levels compared to the edema control value. In accordance, a marked improvement of histopathological findings was observed with both drugs.ConclusionsNAC and verapamil have antinociceptive and anti-inflammatory effects comparable to diclofenac sodium.