Spasmolytic and calmodulin inhibitory effect of non-steroidal anti-inflammatory drugs in vitro
Abstract
The effect of several anti-inflammatory drugs (NSAIDs), the calmodulin inhibitor W-7 and cortisol on vanadate-induced tonic contraction and on calmodulin dependent cAMP-phosphodiesterase activity have been assayed. Indomethacin, diclofenac, phenylbutazone, mefenamic acid, naproxen, tolmetin, piroxicam, aspirin and W-7, but not metimazol, produce dose-dependent relaxation of vanadate-induced tonic contraction on isolated rat uterus. Cortisol relaxes the vanadate contraction up to 45%. None of the drugs assayed inhibit the basal activity of phosphodiesterase with concentrations lower than 1 mM. However, indomethacin, diclofenac, phenylbutazone, mefenamic acid, naproxen, piroxicam, aspirin and W-7 inhibit, in a concentration-dependent way, the calmodulin-stimulated activity of phosphodiesterase. The maximum inhibition achieved with tolmetin (1 mM) and cortisol (1 mM) was 38% and 24%, respectively. Metamizol has no effect on basal or/and stimulated phosphodiesterase. This, as far as we know, is the first description of relationship between NSAIDs and calmodulin-dependent processes and our results suggest that the inhibition of calmodulin with NSAIDs may be directly related to their pKa and liposolubility.
References (26)
- S.B. Abramson et al.
Biochem. Pharmacol.
(1991) - B. Cantabrana et al.
Gen. Pharmac.
(1990) - A.R. Means et al.
Pharmac. Ther.
(1991) - G. Marone et al.
Life Sci.
(1986) - J.A. Sanchez Aparicio et al.
Life Sci.
(1993) - A. Scriabine et al.
Gen. Pharmac.
(1990) - A.I. Fernandez et al.
Gen. Pharmac.
(1992) - M. Gutierrez et al.
Life Sci.
(1994) - S. Abramson et al.
Arthritis Rheumatism.
(1989) - E. Urquhart
Agents Actions
(1991)
N. Eng. J. Med.
Arch. Int. Pharmcodyn. Ther.
Gen. Pharmac.
Cited by (24)
Pharmaceutical wastewater as Emerging Contaminants (EC): Treatment technologies, impact on environment and human health
2022, Energy NexusA wide range of unregulated chemicals of synthetic origin or derived from natural sources, which may be a contender for future regulations are called Emerging Contaminants (ECs). The concentration of ECs ranges from ng/L to μg/L, which is comparatively smaller as compared to other pollutants present in water and wastewater. Even though the environmental concentration is low, ECs still possess a great threat to the humans and ecosystem. These compounds are being widely studied due to their potential health effects, pervasive nature, and difficult degradation through conventional techniques. Pharmaceutical active compounds (PhACs) or pharmaceutical contaminants (PCs) are one of the major groups of ECs which can cause inimical effect on living organisms even at very lower concentration. These contaminants don't degrade easily and persistent for longer periods in the environment due to their stable structure. With the increase in demand of Pharmaceuticals and Personal Care Products (PPCPs), there has been a sharp increase of these pollutants in water bodies. This is mainly due to the inefficiency of conventional wastewater treatment plants in treatment and removal of these PhACs. The proper identification of pharmaceutical groups and development of removal techniques is crucial in the recent times. This review represents a comprehensive summary on PCs, various groups of PCs and an overview of approaches and treatment systems available for their removal. Efficient and effective treatment methods can be useful for completely eradicating these compounds and making the water bodies safe for use. So, the investment of capital and time on research on PCs and their removal techniques can be beneficial for the future.
Adsorption of aspirin and paracetamol from aqueous solution using Fe/N-CNT/β-cyclodextrin nanocomopsites synthesized via a benign microwave assisted method
2015, Journal of Environmental Chemical EngineeringCitation Excerpt :Aspirin and paracetamol are important drugs used by humans and animals [1–3].
Aspirin and paracetamol are used as drugs by animals and humans but are not totally metabolized inside their bodies and hence they often find way into the raw wastewaters. This study presents kinetic and thermodynamic studies of the sorption and removal of aspirin and paracetamol from aqueous solutions using N-CNT/β-CD and Fe/N-CNT/β-CD nanocomposite polymers and the parameters that determine the sorption process. The polymers were prepared via a benign method of microwave-assisted synthesis of the nanocomposites and characterized using Spectrum 100 Fourier transform infrared spectroscopy (FTIR) and focused ion beam scanning electron microscopy (FIB-SEM). The sorption process for aspirin and paracetamol was described by Freundlich and Langmuir isotherms, respectively. The maximum sorption capacities of aspirin and paracetamol onto N-CNTs-β-CD were 71.9 and 41.0 mg g−1 and Fe/N-CNTs-β-CD were 101.0 and 75.2 mg g−1, respectively, at 298 K. The nanocomposites effectively removed aspirin and paracetamol within 30 min of contact time, suggesting that the materials are effective and economically viable. Furthermore, the sorption kinetics of aspirin and paracetamol onto the N-CNT/β-CD and Fe/N-CNT/β-CD sorbents well fitted onto the pseudo second order and Elovich kinetic models, respectively as a minimum SSE was observed. Sorption thermodynamics indicated that the sorption process was feasible, spontaneous and exothermic in nature.
Removal of residual anti-inflammatory and analgesic pharmaceuticals from aqueous systems by electrochemical advanced oxidation processes. A review
2013, Chemical Engineering JournalOccurrence of pharmaceuticals in natural water is considered as an emerging environmental problem owing to their potential toxicological risk on living organisms even at low concentration. Low removal efficiency of pharmaceuticals by conventional wastewater treatment plants requests for a more efficient technology. Nowadays research on advanced oxidation processes (AOPs) have become a hot topic, because these technologies have been shown to be able to oxidize efficiently most organic pollutants until mineralization to inorganic carbon (CO2). Among AOPs, the electrochemical advanced oxidation processes (EAOPs), and in particular, “anodic oxidation” and “electro-Fenton”, have demonstrated good prospective at lab-scale level for the abatement of pollution caused by the presence of residual pharmaceuticals in waters. This paper reviews and discusses the effectiveness of EAOPs for the removal of anti-inflammatory and analgesic pharmaceuticals from aqueous systems.
Uterine relaxant effects of Curcuma aeruginosa Roxb. rhizome extracts
2009, Journal of EthnopharmacologyThe effects and plausible mechanism of action of Curcuma aeruginosa Roxb. (Zingiberaceae) rhizome chloroform and methanol extracts on the uterine contraction were investigated using isolated uterus strips from estrogen primed rats. The contractile responses were recorded isometrically with a Grass FT03 force transducer connected to a MacLab system. The experiments were carried out on both nonstimulated, agonist- and KCl-stimulated uteri. In the nonstimulated uterus, the two extracts (10–400 μg/ml) had no significant effect. In contrast, in the stimulated uterus, the chloroform and methanol extracts exerted concentration-dependent inhibition of the contractions induced by oxytocin (1 mU/ml), prostaglandin F2α (PGF2α, 0.5 μg/ml), ACh (3 × 10−6 M) and KCl (40 mM) with the IC50 (inhibition of force) of 31.4, 58.59, 56.21 and 29.28 μg/ml; and 57.79, 69.3, 223.8 and 69.19 μg/ml, respectively. Verapamil, the reference L-type calcium channel blocker, exhibited a similar pattern of inhibition with the IC50 of 0.03, 0.25, 0.35 and 0.04 μg/ml. The IC50 of diclofenac against a PGF2α-induced contraction was 31.36 μg/ml. It is known that the contraction induced by agonists and KCl is mainly due to calcium influx through the voltage-gated L-type calcium channels opened indirectly or directly by agonist–receptor activation and KCl. Thus, it is speculated that the two plant extracts might inhibit uterine contraction by interrupting the influx of Ca2+ probably through voltage-gated L-type calcium channels. This possibility was further substantiated by the ability of the extracts to shift the CaCl2–contraction curves to the right. As the methanol extract also reduced the contraction of oxytocin in Ca2+-free EDTA solution; thus, it is suggested that part of its action may be involved with an intracellular mechanism. The effect of the two extracts did not involve the activation of β2-adrenoceptors since their effects were unaffected by propranolol. Based on the inhibitory effect of the extracts on the oxytocin-induced contraction, it is concluded that the extracts might be useful as tocolytic agents for the prevention of preterm labor. Their effects on the inhibition of PGF2α-induced contractions also seem useful for the treatment of dysmenorrhea. There are reports by others that the plant rhizome contains β-pinene and sesquiterpenes. In addition, there is evidence that these compounds possess spasmolytic effects in the rat intestine and uterus. Therefore, the uterine relaxant effect of the plant extracts could be due to β-pinene and some sesquiterpene lactones contents. The methanol extract is less potent than the chloroform extract, and this might be due to the lower amount of terpene compounds or different compounds may involve in this action.
Validation of a tubular bismuth film amperometric detector. Determination of diclofenac sodium by multisyringe flow injection analysis
2007, Journal of Pharmaceutical and Biomedical AnalysisCitation Excerpt :At higher pH values the peak potential remained constant. This behaviour may be associated with the acid-base properties of DS (its reported pKa value is 4.0) [34]. The slope value obtained was −54 mV pH−1; the corresponding r2 was 0.992.
A tubular bismuth film electrode (BFE), installed as part of a multisyringe flow injection system, was used as an amperometric detector to determine the concentration of diclofenac sodium in pharmaceutical formulations. A tubular voltammetric detection cell was employed, in which the hydrodynamic flow conditions were not disturbed. This automated method allows the continuous regeneration of the BFE, preventing passivation of the detector and improving the sensitivity of detection. The influence of several variables on this sensitivity, such as the injection volume, deposition time and flow rate were evaluated; a two-level factorial experimental design was employed for this. In optimal conditions, the linear range of the calibration curve varied from 6.0–50.0 μmol L−1, with a detection limit of 4.3 μmol L−1. A sampling rate of 90 determinations/h was achieved; the relative standard deviation of analytical repeatability was <3.5%. After 30 injections the bismuth film on the electrode surface was automatically renewed. The method was validated by comparing the results obtained with those provided by RP-HPLC; no significant difference were seen (p < 0.05).
Naproxen removal from water by chlorination and biofilm processes
2005, Water ResearchNaproxen is an anti-inflammatory pharmaceutical that has been detected in natural and engineered aquatic environments. The primary aim of this research was to study chemical transformations of naproxen following chlorine oxidation, which is common in water and wastewater treatment systems. Synthetic waters containing elevated concentrations of naproxen were oxidized by free chlorine at naproxen:chlorine molar ratios of 0.02–3:1 and pH values of 5–9. The formation of naproxen products was dependent on pH, chlorine dosage and contact time. This study demonstrates that naproxen readily reacts with free chlorine and forms disinfection products. The formation of specific reaction products can vary depending on the characteristics of the water or wastewater and treatment operating conditions. More research is needed to identify intermediate and chemical reaction end products and to understand the reaction kinetics of naproxen chlorination for a range of water and wastewater treatment conditions. A secondary aim of this research was to study effects of naproxen and its chlorination products on biofilm processes, which are common in water and wastewater treatment systems and natural aquatic environments. A bioreactor was fed a naproxen solution and then fed a solution at the same naproxen concentration following contact with free chlorine. Results indicate that naproxen was not degraded biologically for the conditions of this study. In contrast, the naproxen solution containing products of chlorination caused an adverse response by discharging biomass from the bioreactor. Results therefore demonstrate that naproxen products of chlorination can adversely affect a biofilm process, which potentially can impact the performance of biofilm processes in natural and engineered aquatic environments. More research is needed to study naproxen chlorination reactions at low concentrations and in complex matrices, and to understand the toxicological relevance of naproxen and its products of chlorination in natural and engineered aquatic environments.