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At least 145 records · Page 8Linked to original sources
PubMed1995

A randomized, placebo-controlled, double-blind, parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension.

The efficacy and safety of various doses of losartan potassium, a specific and selective angiotensin II receptor antagonist, were compared with those of placebo and enalapril maleate 20 mg in patients with mild to moderate essential hypertension in a randomized, double-blind, parallel study. We randomly allocated 576 patients at the end of a 4-week placebo baseline period to 8 weeks of once-daily double-blind treatment with losartan potassium 10, 25, 50, 100, or 150 mg, enalapril maleate 20 mg, or placebo. After 8 weeks of treatment, mean reductions from baseline in supine systolic/diastolic pressure 24 hours after dosing (trough) for losartan potassium 10, 25, 50, 100, and 150 mg, enalapril maleate 20 mg, and placebo were 7.6/7.9, 7.8/6.8, 13.0/10.1, 8.9/9.9, 10.5/9.7, 14.7/11.2, and 3.8/5.6 mm Hg, respectively. Compared with mean changes in supine diastolic pressure in the placebo group, losartan potassium 50 to 150 mg and enalapril maleate 20 mg produced clinically important and statistically significant reductions (P < or = .01) in blood pressure. At 24 hours after dosing, the blood pressure changes obtained with losartan potassium 50 mg were essentially identical to those obtained with enalapril maleate 20 mg. While there was a dose-related effect with losartan potassium from 10 to 50 mg at peak (6 hours after dosing), doses of 10 and 25 mg were not consistently different from placebo 24 hours after dosing. To assess the once-daily effect of losartan potassium, trough-to-peak ratios of the mean changes in supine diastolic pressure after 8 weeks of treatment were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

The efficacy and safety of timolol maleate versus brinzolamide each given twice daily added to travoprost in patients with ocular hypertension or primary open-angle glaucoma.

PURPOSE: To compare the efficacy and safety of timolol maleate 0.5% versus brinzolamide 1% when added to travoprost 0.004% in patients with ocular hypertension or primary open-angle glaucoma. DESIGN: A prospective, double-masked, randomized, active-controlled, parallel comparison. METHODS: Qualified patients at Visit 1 were placed on travoprost dosed every evening for 4 weeks and then were randomized at baseline (Visit 2) to the addition of timolol maleate or brinzolamide each given twice daily. Patients returned to clinic at Week 4 (Visit 3) for a safety visit and Week 12 (Visit 4) for an efficacy visit. At Visits 2 and 4 the intraocular pressure (IOP) was measured at 08:00, 12:00, and 16:00 hours. RESULTS: Ninety-seven patients on brinzolamide had a baseline diurnal IOP of 21.5+/-2.2 mmHg and 95 on timolol maleate had 21.3+/-2.5 mmHg, each added to travoprost. The diurnal mean IOP at Week 12 was 18.1+/-2.7 mmHg for brinzolamide and 18.1+/-3.0 mmHg for timolol maleate (p=0.96). There was no statistical difference found between treatment groups in the absolute level of pressure, or in the reduction in IOP from baseline, at each time point or for the diurnal curve (p>0.05). There was no significant difference for any adverse event between groups (p>0.05), with the most common side effect being conjunctival hyperemia in 15/97 (16%) brinzolamide and 6/95 (6%) timolol treated patients (p=0.06). CONCLUSIONS: This study showed that brinzolamide provides similar safety and efficacy compared to timolol maleate when added to travoprost.

Antihypertensive Agents↗
PubMedDate not supplied

In vitro characterization of a controlled-release chlorpheniramine maleate delivery system prepared by the air-suspension technique.

Non-pareil cores were spray-coated with a chlorpheniramine maleate (an alkylamine antihistamine) layer and a Eudragit NE30D overcoat in a Wurster air-suspension apparatus. In vitro dissolution studies demonstrated that drug release was a function of polymer membrane thickness. Polyethylene glycol 6000, as a hydrophillic additive, increased the in vitro release of chlorpheniramine maleate from the pellets. Pellets coated with 8.30% Eudragit NE30D, 0.50% talc and 1.00% polyethylene glycol 6000 were found to display desirable controlled release characteristics for chlorpheniramine maleate over the 8-h testing period, which were also comparable with that of Dykatuss capsules. The controlled release pellets exhibited first-order release characteristics for chlorpheniramine maleate. Reproducibility of the manufacturing conditions employed in the study were confirmed thus ensuring reproducibility of drug release characteristics between batches of chlorpheniramine maleate pellets. Drug release from the pellets was shown to be independent of the dissolution method and medium used. Pellets displayed no significant change in drug release characteristics relative to the initial drug release data when stored for 12 weeks at room temperature (20 +/- 2 degrees C) and for 8 weeks at a low temperature (5 +/- 1 degrees C). However, pellets stored at 37 degrees C with 80% relative humidity and at 40 +/- 2 degrees C showed a slower in vitro drug release after 8-week storage and therefore failed to maintain their initial drug release profile.

Capsules↗
PubMed2001

[HPCE determination of trimebutine maleate in rat plasma and its pharmacokinetics].

AIM: To develop a method for the determination of trimebutine maleate in rat plasma by using high performance capillary electrophoresis. The method was employed to pharmacokinetic analysis of trimebutine maleate. METHODS: Plasma samples were deproteinized with acetonitrile (containing ephedrine hydrochloride as internal standard) and the supernatant was dried under N2 stream at 50 degrees C. The residue was dissolved with methanol-water (1:1) and injected into the capillary by siphon. The electrophoresis was performed in uncoated fused-silica capillary and the voltage was 10 kV. The running buffer was 0.03 mol.L-1 NaH2PO4(pH 6.0). The eluate was detected at 214 nm by UV detection. RESULTS: The recovery for trimebutine maleate in rat plasma was 72.8%-87.9%. The calibration curve in plasma was linear over the range 5-200 micrograms.L-1. The limit of quantitation was 5 micrograms.L-1. The intraday relative standard deviation (n = 6) and the interday relative standard deviation (n = 18) were less than 14%. The highest concentration in plasma was observed at 30 min after ig trimebutine maleate to rats. The pharmacokinetic results were AUC0-infinity = 8 micrograms.min.mL-1, T1/2(Ke) = 173 min and Ke = 5.6 x 10(-3) min-1. CONCLUSION: The method is accurate, sensitive and suitable for pharmacokinetic study of trimebutine maleate.

Animals↗
PubMedDate not supplied

Determination of chlorpheniramine maleate and tincture ipecac in dosage form by liquid chromatography with ultraviolet detection.

A procedure was developed and validated for measuring chlorpheniramine maleate and tincture ipecac (as emetine hydrochloride) by reversed-phase liquid chromatography with methanol-10 mM sodium heptanesulfonate (20 + 30) as the mobile phase; the pH was adjusted to 4 with acetic acid, and the flow rate was at 1.5 mL/min, with ultraviolet detection at 254 nm. Propyl paraben was used as the internal standard. The standard curves were linear (r = 0.998 and 0.9998) for both chlorpheniramine maleate and emetine hydrochloride over the ranges of 5-100 and 0.1-40 microg/mL, respectively. The mean recoveries +/- standard deviation were 101.37 +/- 2.77% for chlorpheniramine maleate and 98.8 +/- 1.47% for emetine hydrochloride. The proposed method was applied to the determination of chlorpheniramine maleate alone in tablet and syrup dosage forms. The method also was applied to the determination of the emetine content of ipecac liquid extract and tincture ipecac; the results were compared with those of the method of the British Pharmacopoeia. The proposed method was applied successfully to the simultaneous determination of chlorpheniramine maleate and tincture ipecac, as emetine hydrochloride, in syrup dosage form. Both drugs and the internal standard were separated from all interfering components in < 5 min. The proposed method is simple, specific, and economical, when compared with other published methods that determine each component alone.

Chlorpheniramine↗
PubMedDate not supplied

Simultaneous determination of chlorpheniramine maleate and dexamethasone in a tablet dosage form by liquid chromatography.

An accurate, simple, reproducible, and sensible liquid chromatographic method was developed and validated for the determination of chlorpheniramine maleate and dexamethasone in a tablet formulation. The analysis was performed at room temperature on a reversed-phase C18 column with UV detection at 254 nm. The mobile phase consisted of 7.5 mM monobasic potassium phosphate in methanol-water (62.5 + 37.5) at a constant flow rate of 1 mL/min. The method was validated in terms of linearity, precision, accuracy, and specificity by forced decomposition of chlorpheniramine maleate and dexamethasone initiated by using acid, base, water, hydrogen peroxide, heat, and light. The response was linear in the ranges of 0.04-0.12 and 0.006-0.016 mg/mL for chlorpheniramine maleate (r2 = 0.9999) and dexamethasone (r2 = 0.9994), respectively. The relative standard deviation values for intra- and interday precision studies were 2.39 and 2.02, respectively, for chlorpheniramine maleate and 2.39 and 1.25, respectively, for dexamethasone. Recoveries ranged from 95.07 to 101.95% for chlorpheniramine maleate and from 97.75 to 102.10% for dexamethasone.

Chlorpheniramine↗
PubMed1975

Timolol maleate, a new beta-adrenergic receptor blocking agent.

Some pharmacodynamic properties of an oxypropanolamine substituted novel heterocyclic compound are described. Initial studies involve comparison of the racemic mixture, dl-timolol maleate, with the beta-adrenergic receptor blocking agent propranolol in the rat, dog and cat. dl-Timolol maleate is shown to be a potent inhibitor of cardiovascular beta-adrenergic receptors activated by isoproterenol or adrenergic nerve stimulation. Blockade of alpha-adrenergic receptors is not observed even after extremely high doses. The compound is approximately 3 times more potent than propranolol in suppressing isoproterenol-induced cardioacceleration by the i.v. route of administration. dl-Timolol maleate is also extremely well absorbed when given orally, being then about 10 times more active than propranolol. Unlike propranolol, neither dl-timolol maleate nor its optical isomers possess demonstrable local anesthetic activity. Similar to propranolol and other beta-adrenergic receptor blocking agents, activity of the compound resides predominantly in the l-isomer (timolol maleate.

Adrenergic beta-Antagonists↗
PubMed1987

Analgesic activity following combined oral administration of flupirtine maleate and peripherally acting analgesics in mice and rats.

Concomitant administration of flupirtine maleate at a single low dose (15 mg/kg, mice; 35 mg/kg, rats) with a wide range of doses of each of the peripherally acting analgesics enhanced the antinociceptive activity of paracetamol, acetylsalicyclic acid and ibuprofen in the acetic acid writhing test, acetylsalicylic acid in the hot plate test and paracetamol, acetylsalicyclic acid and ibuprofen in the Randall-Selitto test. The concomitant administration of a single low dose of the peripherally acting analgesics (at about 1/2 ED50) with a wide range of doses of flupirtine maleate resulted in enhancement of flupirtine maleate analgesic activity by paracetamol (in the hot plate and Randall-Selitto tests), acetylsalicyclic acid (in the acetic acid writhing test), ibuprofen (in the Randall-Selitto test) and indomethacin (in the acetic acid and Randall-Selitto tests). Thus flupirtine maleate enhanced the analgesic activity of paracetamol, acetylsalicyclic acid and ibuprofen in mice and rats. Each of the peripherally acting analgesics enhanced the analgesic activity of flupirtine maleate in one or more of the analgesic tests used.

Acetaminophen↗
PubMed1981

[Comparative hepatic toxicity of perhexiline maleate and griseofulvin in mice].

Hepatic toxicity was observed in mice which had received Griseofulvin or Perhexilin Maleate over a period of several months. Treatment of griseofulvin alone gave rise to hepatitis with the presence of Mallory bodies (MB) whereas the same length of treatment with Perhexilin Maleate was associated with steatonecrosis with an absence of MB. When treatment was followed by a one month rest period hepatic lesions disappeared with no trace of sequelae. Cross-treatment studies showed that one week of Perhexiline Maleate was sufficient to induce MB in mice pretreated with Griseofulvin. Similarly, Griseofulvin administered to mice pretreated with Perhexilin Maleate gave rise to MB formation after one week as opposed to the usual two months incubation time (DENK et al.). The histological nature and mode of formation of these MB was identical to that encountered in acute alcoholic hepatitis. On addition, combined drug therapy employing Perhexilin Maleate suggests a particular hepatic toxicity in man in cases where the liver has become predisposed due to other therapeutic.

Animals↗
PubMed1983

Glutathione depletion and in vitro lipid peroxidation in mercury or maleate induced acute renal failure.

Nephrotoxic acute renal failure was experimentally induced in male rats by s.c. application of mercuric chloride and i.p. administration of maleate, respectively. Mercuric chloride and maleate are known to enhance the formation of free radicals and peroxides, which presumably overload the cell's natural elimination mechanisms for these highly reactive intermediates. In addition, a reduction in activities of superoxide dismutase, catalase and glutathione-peroxidase, enzymes responsible for the protection of cells against peroxidative action of superoxide anions and hyperperoxides was found. In both models of acute renal failure, enhanced lipid peroxidation in kidney homogenates in vitro, monitored as malondialdehyde production, was observed. Furthermore, HgCl2 and maleate may react with free SH-groups and thus lead to a depletion of glutathione in tubular cells. Indeed, renal cortical contents of reduced and oxidized glutathione were drastically diminished. These results suggest that alterations in membrane integrity, possibly caused by peroxidative processes, can be considered the cause underlying the well-known disturbances in renal function commonly observed during the initiation phase of HgCl2 and maleate induced acute renal failure.

Acute Kidney Injury↗
PubMed1981

Effect of cysteine, diethyl maleate, and phenobarbital treatments on the hepatotoxicity of [1H]chloroform.

The effects of cysteine, diethyl maleate and phenobarbital treatments and 2H-substitution on the hepatotoxicity of chloroform were investigated. Time course studies of covalent binding and hepatoxicity in phenobarbital-treated rats showed that covalent binding of 14C-label from [14C]chloroform was maximal at 6 h after chloroform administration while hepatotoxicity reached a peak at 18 h. Cysteine treatment reduced both covalent binding and hepatotoxicity, while diethyl maleate and phenobarbital treatments increased both the hepatotoxicity of chloroform and the covalent binding of chloroform metabolites to hepatic proteins. A deuterium isotope effect was present on chloroform-induced hepatotoxicity in diethyl maleate-treated rats suggesting that the previously reported inhibition of haloform metabolism by diethyl maleate occurs at a step in the reaction mechanism after phosgene production. These data support the concept that phosgene is the toxic intermediate in chloroform metabolism.

Alanine Transaminase↗
PubMed1995

Chronic treatment with dizocilpine maleate increases the number of striatal neurons expressing the D2 receptor gene.

N-methyl-D-aspartate antagonists have been proposed as potential therapeutic agents in different neurological diseases, including Parkinson's disease. The effects of gene expression of a chronic treatment with the non-competitive N-methyl-D-aspartate antagonist, dizocilpine maleate (0.8 mg/kg day, per os for 50 days) were analysed in rat striata. Using quantitative in situ hybridization, we measured the messenger RNA expression of the genes encoding D1, D2 dopamine receptors, N-methyl-D-aspartate receptor 1 subunit of N-methyl-D-aspartate receptor, preproenkephalin A and substance P. Chronic treatment with dizocilpine maleate induced a moderate but significant increase in messenger RNA of the N-methyl-D-aspartate receptor 1 subunit in the striatum and the adjacent cortex, suggesting an action of dizocilpine maleate in these two regions. This treatment did not induce any change in D1 receptor, preproenkephalin A or substance P messenger RNA content in the striatum, whereas D2 receptor messenger RNA was increased in the striatum of treated rats. Microscopic analysis revealed that it was the number of medium-sized neurons expressing D2 receptor messenger RNA that was significantly enhanced, while the mean amount of message per cell remained unchanged. These results demonstrate that glutamate via N-methyl-D-aspartate receptors, regulates the D2 receptor gene in striatal neurons. A chronic treatment with dizocilpine maleate increases the number of striatal neurons expressing the D2 receptor gene, suggesting a recruiting phenomenon.

Animals↗
PubMed2005

Phenothiazine maleates stimulate MRP1 transport activity in human erythrocytes.

The expression of multidrug resistance-associated protein (MRP1) results in ATP-dependent reduction of drugs' concentration in cancer cells, i.e., multidrug resistance (MDR). Since the majority of projects are concentrated on the search of the new MDR modulators, there are very few reports on drug-induced stimulation of MDR transporters activity. In the present work, by means of functional fluorescence assay we have shown that MRP1-mediated efflux of 2',7'-bis-(3-carboxypropyl)-5-(and-6)-carboxyfluorescein (BCPCF) out of human erythrocytes is stimulated by phenothiazine maleates that have been already identified as P-glycoprotein inhibitors. Phenothiazine maleates-induced stimulation of ATP-dependent uptake of 2',7'-bis-(3-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) into inside-out membrane vesicles prepared from erythrocyte membranes has been also demonstrated. Moreover, it was shown that phenothiazine maleates exerted stimulating effect on ATPase activity measured in erythrocyte membranes. To our best knowledge, this report is the first one demonstrating that compounds able to inhibit transport activity of P-glycoprotein can stimulate MRP1 transporter. We conclude that phenothiazine maleates probably exert their stimulatory effect on MRP1 by direct interaction with the protein at the site different from the substrate binding site.

Benzbromarone↗
PubMedDate not supplied

Neither lipophilicity nor membrane-perturbing potency of phenothiazine maleates correlate with the ability to inhibit P-glycoprotein transport activity.

Although phenothiazines are known as multidrug resistance modifiers, the molecular mechanism of their activity remains unclear. Since phenothiazine molecules are amphiphilic, the interactions with membrane lipids may be related, at least partially, to their biological effects. Using the set of phenothiazine maleates differing in the type of phenothiazine ring substitution at position 2 and/or in the length of the alkyl bridge-connecting ring system and side chain group, we investigated if their ability to modulate the multidrug resistance of cancer cells correlated with model membrane perturbing potency. The influence exerted on lipid bilayers was determined by liposome/buffer partition coefficient measurements (using the absorption spectra second-derivative method), fluorescence spectroscopy and calorimetry. Biological effects were assessed by a flow cytometric functional test based on differential accumulation of fluorescent probe DiOC(2)(3) by parental and drug-resistant cells. We found that all phenothiazine maleates were incorporated into lipid bilayers and altered their biophysical properties. With only few exceptions, the extent of membrane perturbation induced by phenothiazine maleates correlated with their lipophilicity. Within the group of studied derivatives, the compounds substituted with CF(3)- at position 2 of phenothiazine ring were the most active membrane perturbants. No clear relation was found between effects exerted by phenothiazine maleates on model membranes and their ability to modulate P-glycoprotein transport activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Therapeutic effect of hypothermia and dizocilpine maleate on traumatic brain injury in neonatal rats.

This study was undertaken to evaluate the therapeutic effect of hypothermia and dizocilpine maleate in traumatic brain injury (TBI) on newborn rats. After induction of TBI, physiologic and histopathological assessments were performed on both the control and therapeutic groups to evaluate the effects of both agents. Rats were assigned into four groups as follows: normothermic (n = 23), hypothermic (n = 18), normothermia plus dizocilpine maleate (n = 18) and hypothermia plus dizocilpine maleate (n = 18). All the rats were injured using a weight-drop head injury model, artificially ventilated with a 33% O(2) and 66% NO(2) mixture, and physiological parameters, intracranial pressure, and brain and rectal temperatures were recorded. Mortality, physiological, neurological parameters, and histopathological changes were assessed after 24 h. As a result, intracranial pressure, cerebral perfusion pressure, morbidity, weight loss, and microscopic changes were significantly worse in the normothermic group (p <0.05). There was no statistical difference between other groups (p > 0.05). Hypothermia and dizocilpine maleate displayed similar neuroprotective effects in TBI on newborn rats, but no additive effect was observed.

Animals↗
PubMed2001

Aminopyrimidine-carboxyl(ate) interactions in trimethoprim maleate, an antifolate drug.

In the title cocrystal, trimethoprim maleate [2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidin-1-ium maleate], C(14)H(19)N(4)O(3)(+).C(4)H(3)O(4)(-), the trimethoprim molecule is protonated at N1. The carboxyl group of the maleate ion makes a specific double hydrogen bond of type N-H.O with the 2-amino group and the protonated N1 atom of the trimethoprim cation which is similar to the carboxylate-trimethoprim cation interaction observed in the complex of dihydrofolate reductase with trimethoprim. The pyrimidine moieties of trimethoprim cations are centrosymmetrically paired through a pair of N-H.N hydrogen bonds involving the 4-amino group and the pyridinium N3 atom of a symmetry-related molecule. One of the O atoms at the maleate carboxylate group bridges the 2-amino and 4-amino groups on either side of the paired trimethoprim cations. The other O atom of the carboxylate group forms an intramolecular O-H.O hydrogen bond with the carboxyl group. These characteristic hydrogen bonds result in infinite two-dimensional aggregation of rings into a supramolecular ladder, which is further crosslinked through weak C-H.O interactions with methoxy groups of neighbouring trimethoprim molecules to form a layered structure.

Crystallography, X-Ray↗
PubMed1992

Brush border membrane proteins in experimental Fanconi's syndrome induced by 4-pentenoate and maleate.

Fanconi's syndrome was investigated using brush border membrane (BBM) vesicles isolated from dog kidney. Sodium-dependent uptake of glucose, phosphate, and amino acids and protein phosphorylation were studied in BBM isolated from normal and from 4-pentenoate- and maleate-treated animals. The time course of D-glucose and phosphate uptake, in BBM vesicles, remained unchanged, indicating that both treatments had no effect on carrier properties, and that permeabilities to these substrates and to sodium were not modified. Furthermore, sodium-dependent transport of alanine, phenylalanine, proline, glycine, and glutamate into vesicles remained unaltered by either treatment. 4-Pentenoate treatment caused modifications of the phosphorylation pattern of BBM proteins: the phosphorylation of two proteins (61 and 74 kDa) was increased and that of two others (48 and 53 kDa) was decreased. Maleate treatment caused an increase in the phosphorylation for the same 61-kDa protein, which was also affected by 4-pentenoate treatment, suggesting that phosphorylation of this protein could be related to a mechanism involved in both 4-pentenoate- and maleate-induced Fanconi's syndrome. These changes were also observed in the presence of sodium fluoride and L-bromotetramisole, indicating that the modification of phosphorylation was not due to a difference in phosphatase activities. These results suggest that Fanconi's syndrome induced by 4-pentenoate or maleate is not caused by an inhibition of BBM Na(+)-dependent transport systems. Our results also suggest that protein phosphorylation may play an important role in the molecular defect involved in Fanconi's syndrome.

Animals↗
PubMed1988

Effect of maleate on tubular protein reabsorption in dog kidneys.

To examine the effects on protein and electrolyte reabsorption of reducing the energy supply to the proximal tubules, an inhibitor of the citric acid cycle, maleate (600 mg.kg-1), was administered to anesthetized dogs during continuous ethacrynic acid infusion. One hour after infusion, maleate reduced renal oxygen consumption from 128 +/- 3 to 48 +/- 6 mumol.min-1. Comparisons at similar GFR showed that maleate reduced bicarbonate reabsorption by 65%, chloride reabsorption by 60% and phosphate reabsorption by 90%. Tubular reabsorption of lysozyme, determined by the 'trapped-label' method, was reduced by 97%. Total protein excretion in urine increased from 0.12 to 1.0 mg.min-1 and was not associated with a significant increase in brush border and lysosome marker enzymes. However, by superimposing a carbonic anhydrase inhibitor, acetazolamide (100 mg.kg-1), electrolyte reabsorption was slightly further reduced but protein excretion increased to 2.7 mg.min-1, coincidentally with a dramatic increase in enzyme excretion: approximately 20-fold in the brush border enzymes, alanine aminopeptidase and alkaline phosphatase, and 10-fold in the lysosomal enzymes, acid phosphatase and N-acetyl-beta-glucosaminidase. Our data indicate that maleate stops protein reabsorption without signs of acute tubular damage, whereas subsequent administration of acetazolamide results in tubular desquamation and albumin leakage.

Absorption↗