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Evaluation of "Guia para Dejar de Fumar," a self-help guide in Spanish to quit smoking.

Because of the absence of culturally appropriate self-help smoking cessation materials for Latinos, a new Spanish language cessation guide, "Guia para Dejar de Fumar," was developed and evaluated. It was distributed as part of a community-wide intervention to decrease the prevalence of smoking. The "Guia" is an attractive full-color booklet written in universal Spanish that uses simple text and numerous photographs. Motivation to quit smoking is emphasized, and graphic demonstrations of the adverse health effects of smoking are included. A menu of quitting and maintenance techniques is presented. A total of 431 smokers were identified for evaluation at approximately 3, 6, and 12 months after receiving the "Guia." Self-reported quit rates declined from 21.1 percent at 2.5 months to 13.7 percent at 14 months; 8.4 percent of the sample had a validated quit status by saliva cotinine test at 1 year. Persons older than 44 years were more likely to remain nonsmokers, but sex, education, acculturation score, and cigarettes smoked per day did not predict smoking cessation. The components of the "Guia" most mentioned by those who were surveyed were the graphic photographs, the health emphasis, and the overall format. The authors concluded that the "Guia" is an appropriate self-help smoking cessation booklet for Spanish-speaking Latinos in the United States.

Adolescent↗

[Halidor, 1-benzyl-1-(3'-dimethylaminopropoxy)-cyclohep tane fumarate as an uncoupler and inhibitor of the respiratory chain].

Halidor 1-benzyl-1-(3'-dimethylaminopropoxy)-cycloheptane fumarate, activates succinate oxidation in mitochondria and inhibits reverse electron transport from succinate to NAD+ in submitochondrial partides preparations at doses of 2-10(-5)--10(-3) M. At a dose of 5--7-10(-4) M halidor cause a swelling of mitochondria incubated in 0.1 M NH4NO3. At higher concentrations (10(-3)--10(-2) M) halidor practically completely inhibits NADH and succinate oxidase activity of mitochondria and submitochondrial particles. It is suggested that vasodilating effect of halidor is due to the uncoupling of oxidative phosphorylation, thus causing a deficiency of ATP for contracting function of blood vessel muscles.

Adenosine Triphosphate↗

Pseudo cross-link of human hemoglobin with mono-(3,5-dibromosalicyl)fumarate.

The reaction of human oxyhemoglobin with mono(3,5-dibromosalicyl)fumarate, produces a derivative specifically acylated at the two lysines beta 82, which can be purified with a 70% yield. The oxygen affinity of this derivative at 37 degrees C at pH 7.4, 0.1 M Cl- is of 12 mm Hg, and is not affected by organic phosphate. In the presence of 5% CO2, the oxygen affinity decreases to 25 mm Hg. In all cases the cooperativity is lowered, with a value of n in the Hill plots near 2. Sedimentation velocity measurements indicate that, contrary to normal hemoglobin, this derivative fails to dissociate into dimers upon exposure to pH 5.5. The stability of the tetrameric structure is probably due to a modification of the beta-beta interface, resulting from electrostatic and hydrophobic interactions introduced in the beta cleft by the fumaryl residues. These new interactions are probably the origin of a new reverse Bohr effect group at alkaline pH. Consistent with the stabilization of the tetrameric structure, the half-time of retention of this compound in the rat is increased 4-fold with respect to that of normal hemoglobin. These characteristics cast a favorable light on the usage of this compound as an oxygen carrier in transfusional and perfusional fluids.

Amino Acids↗

Equilibrium oxygen binding to human hemoglobin cross-linked between the alpha chains by bis(3,5-dibromosalicyl) fumarate.

Oxygen equilibrium curves of human hemoglobin Ao (HbAo) and human hemoglobin cross-linked between the alpha chains (alpha alpha Hb) by bis(3,5-dibromosalicyl) fumarate were measured as a function of pH and chloride or organic phosphate concentration. Compared to HbAo, the oxygen affinity of alpha alpha Hb was lower, cooperativity was maintained, although slightly reduced, and all heterotropic effects were diminished. The major effect of alpha alpha-cross-linking appears to be a reduction of the oxygen affinity of R-state hemoglobin under all conditions. However, while the oxygen affinity of T-state alpha alpha Hb was slightly reduced at physiologic chloride concentration and in the absence of organic phosphates, KT was the same for both hemoglobins in the presence of 2,3-diphosphoglycerate (or high salt) and higher for alpha alpha Hb in the presence of inositol hexaphosphate. The reduced O2 affinity arises from smaller binding constants for both T- and R-state alpha alpha Hb rather than through stabilization of the low affinity conformation. All four Adair constants could be determined for alpha alpha Hb under most conditions, but a3 could not be resolved for HbAo without constraining a4, suggesting that the cross-link stabilizes triply ligated intermediates of hemoglobin.

2,3-Diphosphoglycerate↗

[Effect of brovincamine fumarate on cerebral ischemia acutely induced by BLCL in SHRSR].

The present study was designed to clarify the effect of brovincamine fumarate (BV 26-723: BV) on the degree of cerebral ischemia acutely induced by bilateral common carotid artery ligation (BLCL) in stroke-resistant spontaneously hypertensive rats (SHRSR). BV was administered to SHRSR by intraperitoneal infusion (I.P.) of 30 mg/kg (BV 30 mg/kg group), 60 mg/kg (BV 60 mg/kg group) and 0.9% saline was similarly injected to SHRSR (control group) before and immediately after BLCL. Cerebral blood flow (rCBF) in the thalamus was measured by hydrogen clearance technique before and until 3 hr of BLCL periodically. The brain metabolites (ATP, lactate, pyruvate) were determined by the enzymatic method and the brain water content was measured by freeze-dry method 3 hr after BLCL. The histopathological changes in brain vessels were observed by scanning electron microscopy (SEM) 3 hr after BLCL. The rCBF of three groups were identical before BLCL. However, the rCBF of BV 30 mg/kg group was statistically higher than in control group until 2 hr after BLCL, and that of BV 60 mg/kg group was significantly higher even 3 hr after BLCL. In measurements of the brain metabolites after BLCL, ATP and pyruvate levels in both the BV 30 mg/kg and 60 mg/kg groups were statistically higher than the control group. And brain lactate concentrations in both the BV 30 mg/kg and 60 mg/kg groups were significantly lower than the control group. The brain water content of BV 30 mg/kg and 60 mg/kg groups were significantly lower then the control group after BLCL.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Clinical investigation of ketotifen in perennial allergic rhinitis: a double-blind comparative study of ketotifen and clemastine fumarate.

In several clinics we carried out a comparative double-blind study of ketotifen (HC) in 260 patients with perennial rhinitis in order to reveal the clinical efficacy, safety and usefulness. We administered two different doses of HC (0.5 mg X 2 and 1 mg X 2 daily), clemastine fumarate, CF (1.34 mg X 2 daily) and their placebos. The active drugs were always given in combination with their placebos during a period of 4 weeks. The results indicated that HC, especially HC 1 mg X 2, was superior to CF in efficacy and usefulness. Side-effects were mild and the frequency in which they occurred was similar to CF. In contrast to CF, HC showed an efficacy not only in sneezing and nasal discharge but also in nasal obstruction as well.

Clemastine↗

Use of a new oral analgesic, propiram fumarate, in treating postoperative ocular pain.

Fifty hospitalized patients with moderate to severe ocular pain after retinal surgery were treated with the new, potent, oral analgesic, propiram fumarate. Most patients received total daily doses of 50 to 100 mg for one or two days. Pain relief obtained was excellent or good in 92.7% of the observations. Patient and physician acceptance was 96% and 92%, respectively. Only one side effect was seen. Our overall experience was propiram was favorable.

Aged↗

[Therapy of juvenile iron deficiency with bivalent iron dragees (Fe2-fumarate, succinate, sulfate). Controlled double-blind study].

In 53 children with moderate iron deficiency (haemoglobin 7,5 to 12 g/dl) divalent iron salts as tablets (59Fe2+-fumarate, -succinate, -sulfate) were tested versus placebo (controlled double-blind study). Gastrointestinal side effects were most frequently seen with iron succinate (50%) and iron sulfate (25%). Therapeutic success as measured by haemoglobin regeneration was not significantly different among the three iron salts, but significantly more effective than in the placebo group. Children beyond the age of two years mostly refused the application of tablets and should be supplied with liquid preparations.

Anemia, Hypochromic↗

Renal and systemic-hemodynamic response to isovolemic exchange transfusion with hemoglobin cross-linked with bis (3,5-dibromosalicyl) fumarate or albumin.

Experiments were done in anesthetized rats to determine systemic hemodynamic and renal functional effects of isovolemic exchange transfusion with either 5% albumin or hemoglobin cross-linked with bis (3,5-dibromosalicyl) fumarate (XLHb) in volumes ranging from 1 to 6.3 ml.100 gm-1. Hematocrit decreased in proportion to increasing exchange volumes with either fluid. Exchange with increasing volumes of albumin led to progressive decreases in blood pressure. Exchange of 1 ml.100 gm-1 of XLHb was associated with an increase in blood pressure, whereas with larger exchanges, blood pressure returned to and was maintained at control values even for exchanges as large as 6.3 ml.100 gm-1. An increase of similar magnitude in glomerular filtration rate occurred with both fluids. Net and fractional sodium excretion (FENa) increased significantly with both transfusion fluids; the increase was significantly larger for XLHb than for albumin. Maximal FENa excretion with albumin was about 8% but exceeded 6% with XLHb. Pretreatment with indomethacin (5 mg.kg-1.day-1 for 3 days) did not blunt the diuresis that occurred with an exchange of 2 ml.100 gm-1 XLHb. It is concluded that 5% XLHb, as compared with 5% albumin, better supports systemic blood pressure, especially as exchange volume increases, possibly as a result of hemoglobin-induced increased vascular tone. Although a decrease in hematocrit may play a role in the diuresis observed with either fluid, the greater diuresis with XLHb must be due to some additional factor; the mechanism does not appear to involve prostaglandins.

Animals↗

Calcium antagonistic vasodilator mechanisms of brovincamine fumarate studied in canine cerebral artery.

In order to elucidate the major mechanism of cerebral vasodilator action of brovincamine fumarate (CAS 57475-17-9) the present study was performed comparing its effects with those of d-cis-diltiazem in the isolated canine basilar artery. Brovincamine possessed a wide spectrum of inhibitory actions on the contractions of the artery produced by various spasmogens and mechanical stretch. Brovincamine was 3 to 40 times less potent than d-cis-diltiazem in the inhibitory actions. Simultaneous recordings of intracellular Ca2+ concentration and mechanical activity showed that brovincamine and d-cis-diltiazem decreased both parameters augmented by high KCl in a concentration-dependent and parallel manner. Both brovincamine and d-cis-diltiazem shifted parallel to the right the concentration-response curves for CaCl2-induced contraction of the artery constructed in the Ca(2+)-free depolarizing medium. Furthermore, Schild regression of the curves was linear with a slope of unity, indicating apparently a competitive antagonism between Ca2+ channel function/Ca2+ and brovincamine or d-cis-diltiazem. The results suggest that the cerebral vasodilator effect of brovincamine is mainly attributable to the inhibition of Ca2+ influx through the voltage-dependent Ca2+ channels, supporting the reported clinical benefits of this drug in the treatment of cerebrovascular disorders.

Animals↗

Clemastine fumarate as an antipruritic agent in pruritic cats: results of an open clinical trial.

Clemastine fumarate was administered to 10 presumed or proven atopic cats to determine its efficacy in controlling their pruritus. Initially, each cat received 0.34 mg orally every twelve hours for 14 days. When none responded satisfactorily, the dosage was increased to 0.68 mg/cat every twelve hours. At that dosage, the pruritus in five cats (50%) was eliminated. Diarrhea was seen in one cat. Under the conditions of the study, clemastine was a useful antipruritic agent for the cat.

Administration, Oral↗

Effects of mebendazole, albendazole, and praziquantel on succinate dehydrogenase, fumarate reductase, and malate dehydrogenase in Echinococcus granulosus cysts harbored in mice.

Echinococcus granulosus cyst wall possess high biochemical activities of malate dehydrogenase (MD) and fumarate reductase (FR), but low activity of succinate dehydrogenase (SD), suggesting that the cyst wall may utilize a partial reverse tricarboxylic acid cycle. When infected mice were given intragastrically with mebendazole, 25-50 mg.kg-1.d-1, albendazole 300 mg.kg-1.d-1 or praziquantel 500 mg.kg-1.d-1 for 7-14 d, no apparent effects on SD and FR activities of the cyst wall were found, while the MD activity was suppressed by all the 3 drugs, the inhibition rates being 34.6-61.6%, 59.8%, and 50.6%, respectively. The results suggested that MD may not be an important target for the antihydatidosis drugs.

Albendazole↗

Neuropsychologic and cardiovascular effects of clemastine fumarate under pressure.

Allergic rhinitis and mild respiratory infections have been widely accepted as temporary contraindications for fitness to dive. Nonetheless, several sport and professional divers use antihistamines to ease ear, nose, and throat (ENT) problems, especially for opening tubal ostium. Some divers know they are unfit to dive, but for a variety of reasons (e.g., money or short holiday) they try to clear their ears. Thus, the use of antihistaminic drugs (like clemastine fumarate) is common during diving. This double-blind, crossover study indicates that this special antihistamine does not increase the sedative effects of nitrogen narcosis, nor does it increase the level of cardiac arrhythmias. Liberal use of antihistamines while diving cannot be recommended because of possible complications connected with different preparations and the temporary limitations they impose on the diver.

Adult↗

Effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1 -H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, on impaired learning and memory in animal models.

We examined the effects of p.o. administered 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8- yl)-1-propanone fumarate (TAK-147), a novel AChE inhibitor, on impaired learning and memory in animal models. At 1 to 3 mg/kg, TAK-147 ameliorated the passive avoidance deficit induced by diazepam. TAK-147 did not affect delayed-matching-to-position (DMTP) performance of normal rats at doses of 1 to 30 mg/kg assessed by using a three-lever operant chamber, but 9-amino-tetrahydroacridine disrupted the DMTP response at 5 to 20 mg/kg. Scopolamine (0.02-0.1 mg/kg s.c.) impaired DMTP performance, whereas methylscopolamine did not affect the DMTP task. TAK-147 ameliorated the impairment of DMTP performance induced by scopolamine without affecting the general behavior of the rats; however, 9-amino-tetrahydroacridine produced no significant amelioration of the impairment. The intraventricular injection of AF64A disrupted differential-reinforcement-of-low-rate 10-sec performance in rats, as demonstrated by marked decreases in reinforcement rate and response efficiency. TAK-147 slightly increased the reinforcement rate in AF64A-treated rats at a low dose of 1 mg/kg, but the effect was not significant statistically. TAK-147 had no significant effect on the duration of immobility in rats in a forced swimming test at doses of 2 to 10 mg/kg. 9-Amino-tetrahydroacridine prolonged the duration of immobility at 5 to 20 mg/kg. Furthermore, TAK-147 reversed reserpine-induced hypothermia and ptosis in mice at doses of 3 to 10 mg/kg, a result that implies an antidepressant-like action. These results indicate that TAK-147 ameliorates learning and memory impairment in animal models without affecting the general behavior or causing behavioral depression and suggest that TAK-147 may be useful for the treatment of Alzheimer's disease.

Acetylcholinesterase↗

[Biomimetic oxidation of clemastine hydrogen fumarate].

The reaction of clemastine fumarate (1) with the biomimetic system manganese(III)-5,10,15,20-tetrakis(pentafluoro-water. The reaction of 1 in aqueous solution with manganese(III)-5,10,15,20-tetrakis (pentafluorophenyl)-beta-tetrasulfonatoporphyrin chloride (MnTPFPS4PCl) as catalyst additional generates products of aromatic hydroxylation. Products were identified by TLC, UV, and MS. Thereby we found a close conformity with rat metabolism.

Animals↗

Neurochemical effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-b enzazepin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase inhibitor, in rats.

We examined the neurochemical effects of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzaze pin-8-yl)-1-propanone fumarate (TAK-147), a novel acetylcholinesterase (AChE) inhibitor in vitro and in vivo. TAK-147 showed a potent and reversible inhibition of AChE activity in homogenates of the rat cerebral cortex (IC50 = 51.2 nM), and was 3.0- and 2.4-fold more potent than tacrine and physostigmine, respectively. By contrast, TAK-147 was the least potent inhibitor of butyrylcholinesterase activity in rat plasma (IC50 = 23,500 nM). Tacrine and physostigmine inhibited butyrylcholinesterase activity potently and nonselectively. TAK-147 showed a moderate inhibition of muscarinic M1 and M2 receptor binding with K(i) values of 234 and 340 nM, respectively. TAK-147 showed very weak or no inhibition of high-affinity choline uptake, nicotinic receptor binding and choline acetyltransferase activity. In ex vivo experiments, oral administration of TAK-147 at doses ranging from 1 to 10 mg/kg induced a statistically significant and dose-dependent decrease in AChE activity in the cerebral cortex. Of the monoaminergic systems, TAK-147 moderately inhibited uptake of noradrenaline and serotonin with IC50 values of 4020 and 1350 nM, respectively. TAK-147 also inhibited ligand binding at alpha-1, alpha-2 and serotonin 2 receptors with K(i) values of 324, 2330 and 3510 nM, respectively, whereas it showed only weak activities on D1, D2 and serotonin 1A receptor bindings. Oral administration of TAK-147 (3 mg/kg) significantly accelerated the turnover rates of dopamine, noradrenaline and serotonin in the rat brain. These results suggest that TAK-147 activates the central cholinergic system by specific inhibition of AChE activity without affecting peripheral butyrylcholinesterase activity, and that TAK-147 also moderately activates the monoaminergic systems.

Acetylcholinesterase↗

Pharmacokinetics of ferrous fumarate in rats.

There have been evaluated changes of iron concentration in serum dynamics after single oral administration of ferrous fumarate to rats. Pharmacokinetics parameters were determined and the results were compared to those ferric gluconate.

Administration, Oral↗

[Effects of brovincamine fumarate on choroidal blood volume in rabbits].

We examined the effects of brovincamine fumarate, a Ca(2+)-channel blocker, on choroidal blood flow. We measured the choroidal blood volume continuously for 1 hour using laser Doppler flowmetry, as well as systemic blood pressure, heart rate, and intraocular pressure in six urethane-anesthetized rabbits after intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine. As a control, ten rabbits receiving no medication were used. All the data were recorded and analyzed using MacLab on a computer. In both the 0.1 mg/kg and 0.5 mg/kg brovincamine-injected groups, the choroidal blood volume decreased significantly after administration, but showed no significant difference from controls. Vascular resistance in the choroid showed a significant increase over the value before administration and over the control group. The heart rate decreased significantly compared to the value before injection and to the control group. The mean blood pressure in both dose groups and the intraocular pressure in the 0.5 mg/kg injected group were significantly higher than the controls. These results indicate that intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine does not cause an increase in the choroidal blood volume in urethane-anesthetized rabbits.

Animals↗