Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this research was to characterize by X-ray crystallography the ternary dimethylformamide (DMF) Cu(II) complex of acetylsalicylic acid (aspirin), in an effort to compare the structure-activity relationships for the anticonvulsant activity of this and other Cu(II)aspirinate chelates. The ternary DMF Cu(II) complex of aspirin was synthesized and crystals grown from a DMF solution were characterized by single crystal X-ray diffraction. This crystalline material was analyzed for anticonvulsant activity in the Maximal Electroshock (MES) Grand Mal and subcutaneous Metrazol (scMET) Petit Mal models of seizure used to detect anticonvulsant activity. The ternary DMF complex was found to be a monomolecular binuclear complex, tetrakis-mu-(acetylsalicylato)bis(dimethylformamido)dicopper(II) [Cu(II)(2)(aspirinate)(4)(DMF)(2)] with the following parameters: monoclinic, space group P2(1)/n, a=12.259 (1), b=10.228 (1), c=16.987 (1) A, beta=92.07 (1) degrees; V=2128.5 (3) A(3); Z=2. The structure was determined at 180 K from 2903 unique reflections (I>1sigma(I)) to the final values of R=0.030 and wR=0.033 using F. This binuclear complex contains four acetylsalicylate bridging ligands which are related to each other in a two by two symmetry center. The four nearest O atoms around each Cu atom form a closely square planar arrangement with the square pyramidal coordination completed by the dimethylformamide oxygen atom occupying an apical position at a distance of 2.154 (1) A. Each Cu atom is displaced towards the DMF ligand by 0.187 A from the plane of the four O atoms. Electron paramagnetic resonance (EPR) spectra of [Cu(II)(2)(aspirinate)(4)(DMF)(2)] crystals show a strong antiferromagnetic coupling of the copper atoms, similar to that observed with other binuclear copper(II)salicylate compounds. Studies used to detect anticonvulsant activity revealed that [Cu(II)(2)(aspirinate)(4)(DMF)(2)] was an effective anticonvulsant in the MES model of seizure but ineffective against scMET-induced seizures. The monomolecular ternary binuclear [Cu(II)(2)(aspirinate)(4)(DMF)(2)] complex is more effective in inhibiting MES-induced seizures than other binuclear or mononuclear Cu(II) chelates of aspirin including: binuclear polymeric [Cu(II)(2)(aspirinate)(4)], [Cu(II)(2)(aspirinate)(4)(H(2)O)], which is anticipated to be less polymeric, and monomolecular ternary [Cu(II)(2)(aspirinate)(4)(DMSO)(2)] and [Cu(II)(aspirinate)(2)(Pyr)(2)]. These and other chelates appear to be more effective in the scMET model of seizure than [Cu(II)(2)(aspirinate)(4)(DMF)(2)]. These structure-activity relationships support the potential efficacy of Cu chelates of aspirin in treating epilepsies.
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PMID:Low-temperature (180 K) crystal structure, electron paramagnetic resonance spectroscopy, and propitious anticonvulsant activities of CuII2(aspirinate)4(DMF)2 and other CuII2(aspirinate)4 chelates. 1288 73

Dimethyl sulfoxide (DMSO) has been widely used in the treatment of arthritis and certain inflammatory diseases, and is also considered an alternative remedy for cancer even if not supported by concrete evidence. This report illustrates the first case of a fatal complication following the illicit use of this agent. A 55-y-old man who reportedly ingested 500 mg acetaminophen and approximately 1 ml DMSO solution was brought to the emergency department after experiencing 2 tonic-clonic seizures. He had been diagnosed with lung mesotelioma with brain metastases which caused no neurologic deficit. The ingested DMSO was the first dose within the last 3 mo. Examination revealed right-sided hemiplegia. Unenhanced computed tomography of the head showed 3 hemorrhagic areas with blood-cerebrospinal fluid at the left parietal, occipital and frontal regions accompanied by a midline shift. Despite initial resuscitation, 2 units of fresh frozen plasma and antiedema treatment, the patient experienced cardiac arrest that did not respond to resuscitative measures. DMSO can cause massive intrametastatic hemorrhage, and neurologic deterioration can be profound in patients with metastatic brain lesions.
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PMID:Massive intracranial hemorrhage associated with the ingestion of dimethyl sulfoxide. 1517 90

Following observations that bis(3,5-diisopropylsalicylato)diaquazinc(II), [Zn(II)(3,5-DIPS)(2)(H(2)O)(2)], had anti-convulsant activity, bis(acetylsalicylate)diaquazinc(II), [Zn(II)(aspirinate)(2)(H(2)O)(2)], and the Zn(II) ternary 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neocuproine, NC) or dimethyl sulfoxide (DMSO) complexes of Zn(II)3,5-diisopropylsalicylate, salicylate, and acetylsalicylate were synthesized and spectroscopically characterized. Anti-convulsant and Rotorod toxicity activities of these complexes were determined to examine their anti-convulsant and undesirable central nervous stimulant or depressant activities of these Zn(II) non-steroidal anti-inflammatory agent complexes. Bis(3,5-diisopropylsalicylato)-1,10-phenanthorlinezinc(II), [Zn(II)(3,5-DIPS)(2)(phen)], (1) has one bidentate phen ligand and two mono-deprotonated 3,5-DIPS ligands. One of the carboxylates bonds in an asymmetric chelating mode. The Zn(II) atom exhibits a distorted bicapped rectangular pyramidal environment N(2)O(2)OO (4+1+1 *). In the neocuproine complex, bis(3,5-diisopropylsalicylato)-2,9-dimethyl-1,10-phenanthorlinezinc(II), [Zn(II)(3,5-DIPS)(2)(NC)] (2), the Zn(II) atom has a much more distorted bicapped rectangular pyramidal environment, N(2)O(2)O(2) (4+2 *), compared to 1. The two carboxylate ligands exhibit the same asymmetric coordinating mode with longer metalloelement-oxygen bond distances compared to 1. The space group of [Zn(II)(aspirinate)(2)(H(2)O)(2)] (3), which has been reported as Cc is corrected to C2/c. The zinc atom exhibits a (4+2 *) bicapped square pyramidal environment. While the two ternary phenanthroline-containing complexes, 1 and 2, evidenced weak protection against maximal electroshock (MES)- and subcutaneous Metrazol (scMET) induced seizures, [Zn(II)(3,5-DIPS)(2)(DMSO)(2)], [Zn(II)(aspirinate)(2)(H(2)O)(2)], and bis(salicylato)-1,10-phenanthorlinezinc(II), [Zn(II)(salicylate)(2)(phen)], were found to be particularly useful in protecting against MES and scMET seizures and [Zn(II)(aspirinate)(2)(H(2)O)(2)] and [Zn(II)(salicylate)(2)(phen)] were found to have activity in protecting against Psychomotor seizures, without causing Rotorod toxicity. Activities of these and other Zn(II) complexes of non-steroidal anti-inflammatory agents are consistent with the well-known anti-inflammatory responses of Zn(II)-dependent enzymes. There was also some evidence of Rotorod toxicity consistent with a mechanism of action involving sedative-hypnotic activity of recognized anti-epilepticdrugs.
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PMID:Synthesis, crystal structures, and anti-convulsant activities of ternary [Zn(II)(3,5-diisopropylsalicylate)(2)], [Zn(II)(salicylate)(2)] and [Zn(II)(aspirinate)(2)] complexes. 1552 1

Two pseudopolymorphs, solvates, of [Cu(2)(II)(niflumate)(4)(H(2)O)(2)] of unknown structure were obtained following solution of [Cu(2)(II)(niflumate)(4)(H(2)O)(2)] in N,N-dimethylacetamide (DMA) or N,N-dimethylformamide (DMF). Low-temperature crystal structures obtained for these solvates revealed that they were ternary aqua DMA and DMF solvates: [Cu(2)(II)(niflumate)(4)(H(2)O)(2)].4DMA and [Cu(2)(II)(niflumate)(4)(H(2)O)(2)].4DMF. Intermolecular hydrogen bonding interactions account for the formation of these stable DMA and DMF solvates. These pseudopolymorphs contain a centrosymmetric binuclear center with Cu-Cu bond distances ranging from 2.6439(7) to 2.6452(9) A; the coordination sphere of Cu(II) is characterized by one long Cu-O (water) bond length of 2.128(3)-2.135(3) A and four short Cu-O (carboxylate) bonds of 1.949(3)-1.977(3) A. Crystal parameters for the DMA pseudopolymorph: a=10.372(1), b=19.625(2), c=17.967(2) A, beta=97.40(1) degrees , V=3626.8(6) A(3); monoclinic system; space group: P2(1)/a and for the DMF pseudopolymorph: a=10.125(2), b=18.647(3), c=19.616(4) A, alpha=74.38(2)(o), beta=88.18(2)(o), gamma=79.28(2)(o), V=3504(1) A(3); triclinic system; space group: P1. EPR spectra of these solids are identical and show strong antiferromagnetic coupling between the copper atoms, similar to the spectrum obtained for [Cu(2)(II)(niflumate)(4)(DMSO)(2)]. The [Cu(2)(II)(niflumate)(4)(H(2)O)(2)], [Cu(2)(II)(niflumate)(4)(H(2)O)(2)].4DMA, [Cu(2)(II)(niflumate)(4)(H(2)O)(2)].4DMF, [Cu(2)(II)(niflumate)(4)(DMF)(2)], and[Cu(2)(II)(niflumate)(4)(DMSO)(2)] evidenced protection against maximal electroshock-induced seizures and Psychomotor seizures at various times after treatment, consistent with the well known antiinflammatory activities of Cu chelates, but failed to protect against Metrazol-induced seizures while evidencing some Rotorod Toxicity consistent with a mechanism of action involving sedative activity.
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PMID:Low-temperature (180 K) crystal structures of tetrakis-mu-(niflumato)di(aqua)dicopper(II) N,N-dimethylformamide and N,N-dimethylacetamide solvates, their EPR properties, and anticonvulsant activities of these and other ternary binuclear copper(II)niflumate complexes. 1562 Dec 67

Changes in gonadal steroid hormone levels during the menstrual cycle affect seizure frequency in women with catamenial epilepsy. Since GABA(A) receptors (GABARs) contribute to the prevention and termination of seizures by reducing neuronal excitability, we hypothesized that fluctuating gonadal steroid levels might affect GABAR subunit expression, which could alter inhibitory tone leading to increased seizure activity. To address this question in a simplified environment in vitro, we examined the effects of gonadal steroids on NT2-N neuronal cells. We have previously shown that NT2-N cells express functional GABARs, and that the expression pattern of GABAR subunits is regulated by chronic benzodiazepine exposure and hypoxia. NT2-N neurons were exposed to progesterone (0.1 microM), beta-estradiol (3 nM), or vehicle (DMSO) for 2 days or 7 days prior to RNA harvesting. GABAR subunit mRNA levels were assessed by semiquantitative RT-PCR normalized to actin levels. Progesterone exposure for 7 days increased alpha2 and gamma3 and decreased alpha5 subunit mRNAs, while beta-estradiol caused significant increases in alpha3, beta3 and epsilon expression. Further analysis revealed differential regulation of alpha4, alpha5, epsilon and pi subunit expression. Plots of relative PCR density in progesterone-treated cells for alpha2 vs. alpha5, alpha5 vs. gamma3 and alpha2 vs. gamma3 showed correlation between samples, suggesting coordinate regulation. Both progesterone and estrogen nuclear receptor mRNAs were detected by RT-PCR, and 2 days but not 7 days estrogen exposure upregulated progesterone receptor mRNA. Gonadal steroid fluctuations regulate GABA(A) receptor subunit expression in NT2-N cells. Such changes, if observed in vivo, could affect seizure frequency.
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PMID:Gonadal steroids regulate GABAA receptor subunit mRNA expression in NT2-N neurons. 1600 Feb 29

This study examines the effects of ethanol on lindane-induced seizures in rats. The animals were divided into following groups: 1. saline, 2. DMSO (dimethylsulfoxide), 3. lindane dissolved in DMSO in the dose of 4, 6 or 8 mg/kg (L(4), L(6) and L(8) groups, respectively), 4. ethanol 2 g/kg administered 30 min prior to lindane (protected groups AL(4), AL(6) and AL(8)) and 5. ethanol alone (2 g/kg). In order to determine ethanol concentration in plasma, blood samples were collected by cardiac puncture 30 and 60 min after ethanol injection. For EEG and power spectra recordings, electrodes were implanted into the skull. The lindane treatment resulted in a dose-dependent increase of seizure incidence and severity. The rats displayed severe seizure patterns characterized by high voltage spike-wave complexes, poly-spikes and sleep-like patterns in EEG, while the power spectra were intensively elevated in comparison to the corresponding controls. Ethanol alone led to increased EEG power spectra, which became dominant in the range of 0-4 Hz. For evaluation of anticonvulsant ethanol action we compared latency to seizure, incidence and seizure severity (scale from 0 to 4) in the examined groups. Ethanol diminished seizure incidence in AL(4) and AL(6) groups, decreased intensity of convulsions, and prolonged duration of latency period in AL(8) group. We observed suppression of the EEG signs of lindane-provoked epileptiform activity in AL(4) and AL(6), but not in AL(8) group. These results suggest that ethanol acted protectively on lindane-induced seizures and suppressed behavioral and epileptic EEG spiking activity.
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PMID:Ethanol suppressed seizures in lindane-treated rats. Electroencephalographic and behavioral studies. 1819 78

We report a study on the relation between open-field behavior and electroencephalographic (EEG) changes during lindane-induced seizures in 2-month-old adult male Wistar rats. For chronic EEG recordings and power spectra analysis, 3 electrodes were implanted into the skull. Three groups of animals, (i) saline-injected control (n = 6), (ii) DMSO-treated (n = 6), and (iii) lindane intraperitoneally administered: L(4) (4 mg/kg, n = 10), L(6) (6 mg/kg, n = 11), and L(8) (8 mg/kg, n = 11), were observed for 30 min for the occurrence of convulsive behavior. It was assessed by incidence of motor seizures, and seizure severity grade was determined by a descriptive rating scale (0, no response; 1, head nodding, lower jaw twitching; 2, myoclonic body jerks, bilateral forelimb clonus with full rearing; 3, progression to generalized clonic convulsions followed by tonic extension of fore and hind limbs and tail; 4, status epilepticus). EEG signal and spectral analyses were suitable to describe the dynamics of complex behavioral responses. Incidence and severity of epileptic manifestations, recorded as high voltage spike-wave complexes, polyspikes, sleep-like patterns in EEG, and power spectra changes, were greater in lindane-treated groups in a dose-dependent manner compared with control or DMSO-treated groups. Our results suggest good correlation between lindane-induced epileptiform activity and behavioral changes.
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PMID:Correlation between electrocorticographic and motor phenomena in lindane-induced experimental epilepsy in rats. 1841 26

Diphenyl diselenide [(PhSe)2], an organoselenium compound, presents pharmacological and toxicological properties in rodents. The aim of this study was to carry out the determination and quantification of (PhSe)2 in plasma after oral administration (p.o.) of this compound (500 mg/kg), dissolved in canola oil, in rats and mice. The second objective was to verify the involvement of different routes of administration ((p.o.), intraperitoneal (i.p.) and subcutaneous (s.c.)) and vehicle solutions (canola oil and dimethyl sulfoxide (DMSO)) in the appearance of seizure episodes and in the plasmatic levels of (PhSe)2 in rats and mice. Analysis of (PhSe)2 in blood samples was performed by gas chromatography/flame ionized detector system (GC/FID). Rat and mouse peak plasma (PhSe)2 levels were 13.13 and 10.11 microg/ml (C(max)), respectively, and occurred at 0.5h (T(max)) post-dosing. The use of different administration routes (p.o., i.p. and s.c.) and vehicle solutions (canola oil or DMSO) in rats and mice indicated that the appearance of seizures and (PhSe)2 plasmatic levels are dependent of administration routes (i.p.>p.o.>s.c.), vehicle solutions (DMSO>canola oil) and animal species (mice>rat).
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PMID:Convulsant effect of diphenyl diselenide in rats and mice and its relationship to plasma levels. 1942 94

The aim of this study was to investigate the dynamics of lipid peroxidation and the possible correlation between lipid peroxidation in different brain regions and behavioral manifestations in lindane-induced seizures in rats. Male Wistar rats were divided into the following groups: 1. control, saline-treated group; 2. dimethylsulfoxide (DMSO)-treated group; 3. lindane-treated group (8 mg/kg), intraperitoneally. Animals were sacrificed 0.5 or 4 h after treatment and the malondialdehyde level and superoxide dismutase (SOD) activity were determined in various brain regions spectrophotometrically. Behavioral changes were classified according to the descriptive scale (0--no response, 1--head nodding, lower jaw twitching; 2--myoclonic body jerks, bilateral forelimb clonus with full rearing; 3--progression to generalized clonic convulsions followed by tonic extension of fore- and hind limbs and tail; 4--status epilepticus). A significant rise in the malondialdehyde level was detected in the cerebral cortex, hippocampus, and thalamus of lindane-treated animals 0.5 and 4 h after administration (P < 0.05). SOD activity (total and mitochondrial) was significantly decreased in the hippocampus and the cortex of lindane-treated animals at both time points (P < 0.05). An initial fall in SOD activity was detected in the thalamus 4 h after lindane administration (P < 0.05). A positive correlation between seizure severity and the malondialdehyde level was found in the hippocampus at both time points (P < 0.01). These results suggest that lipid peroxidation may contribute to the neurotoxic effects of lindane in early acute lindane intoxication and that behavioral manifestations correlate with lipid peroxidation in the hippocampus of lindane-treated rats.
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PMID:The correlation between lipid peroxidation in different brain regions and the severity of lindane-induced seizures in rats. 1969 53

Electron spin resonance (ESR)-silent ascorbate solutions generate a detectable, likely concentration-dependent signal of ascorbyl free radicals (AFR) immediately upon addition of a molar excess of dimethyl sulfoxide (DMSO). We aimed to perform quantitative ESR analysis of AFR in real time after addition of DMSO (AFR/DMSO) to evaluate ascorbate concentrations in fresh hippocampus or plasma following systemic administration of kainate in mice. Use of a special tissue-type quartz cell allowed immediate detection of AFR/DMSO ESR spectra in fresh tissues from mice. AFR/DMSO content was increased significantly in fresh hippocampus or plasma obtained during kainate-induced seizures of mice, reaching maximum levels at 90 min after intraperitoneal administration of 50 mg/kg kainic acid. This suggests that oxidative injury of the hippocampus resulted from the accumulation of large amounts of ascorbic acid in the brain after kainic acid administration. AFR/DMSO content measured on an ESR spectrometer can be used for real-time evaluation of ascorbate content in fresh tissue. Due to the simplicity, good performance, low cost and real-time monitoring of ascorbate, this method may be applied to clinical research and treatment in the future.
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PMID:An electron spin resonance study for real-time detection of ascorbyl free radicals after addition of dimethyl sulfoxide in murine hippocampus or plasma during kainic acid-induced seizures. 2033 68


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