Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This double-blind, randomised multicentre study compares nifedipine gastrointestinal therapeutic system (GITS) with atenolol in 129 male patients, with exercise-induced angina pectoris. At 4 weeks, there was no significant difference between nifedipine GITS 60 mg o.d. and atenolol 100 mg o.d., in respect of improved time to onset of 0.1 mV ST-segment depression, time to onset of pain, and total exercise time. Atenolol, but not nifedipine, significantly reduced heart rate and systolic blood pressure at rest and during exercise. There were significantly more vasodilator-related side effects with nifedipine. Nifedipine GITS and atenolol as once-daily monotherapy are equally effective and safe, but have different effects on exercise parameters.
 ...
PMID:Monotherapy with nifedipine GITS compared with atenolol in stable angina pectoris. The Working Group on Cardiovascular Research (WCN). 951 1

In order to compare the efficacy of nifedipine gastrointestinal therapeutic system (GITS) with diltiazem, 99 patients with chronic stable angina were studied in a parallel-group randomised trial. According to the results of the two exercise tolerance tests (ETTs) performed during the placebo run-in, patients were divided into a fixed threshold group if the variability in time to 1 mm ST-segment depression was 20%, or a variable threshold group if it was higher. Efficacy was assessed by comparing the time to 1 mm ST-depression on a bicycle ETT after 4 weeks of treatment, adjusting for the baseline value. The adjusted means were 7.44 min for nifedipine GITS and 7.68 min for diltiazem; the difference was -0.24 min, with a lower 90% confidence limit of -0.90, which is within the stated interval for equivalence. The same result was confirmed by the 'intention-to-treat' analysis, and comparable results were obtained both in fixed and in variable threshold groups. The incidence of side effects was 12% with nifedipine GITS and 8.2% with diltiazem. Nifedipine GITS and diltiazem were found to be equally effective in increasing exercise tolerance in chronic stable angina patients.
 ...
PMID:Nifedipine GITS versus diltiazem in chronic stable angina: a randomised multicentre study. 951 5

L-type voltage-dependent calcium channel blockers acting at different sites were tested in animal models of depression. Their effects on locomotion were studied in separate experiments. Nifedipine, a drug which interacts selectively with dihydropyridine (DHP) binding sites, reduced immobility time in the mouse forced swimming test and tail suspension test, but lacked activity in the differential-reinforcement-of-low-rate schedule in rats (DRL 72 s). The effects of nifedipine in the tail suspension test was partly antagonized by Bay K 8644, a DHP channel activator, indicating that its effect involved L-type calcium channel. Several other DHP drugs (nicardipine, nitrendipine, isradipine, felodipine and nimodipine) also showed antidepressant-like properties in the tail suspension test, whereas amlodipine, a less selective compound, lacked activity. In contrast to the DHP drugs, verapamil and (-)emopamil (which act at the phenylalkylamine binding sites), diltiazem and clentiazem (benzothiazepine binding sites), and the non-selective drug, flunarizine, were inactive in the tail suspension test. Negative results were also obtained with verapamil, diltiazem and flunarizine in the forced swimming test and with flunarizine on DRL 72 s responding. The present results show that DHP channel blockers displayed 'antidepressant-like' properties in mice. There was little dissociation, however, between the doses that produced antidepressant effects and those that decreased locomotor activity.
 ...
PMID:Assessment of the antidepressant-like effects of L-type voltage-dependent channel modulators. 983 75

Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides stable plasma concentrations over the entire 24 h dosing interval. Two-hundred and one patients with Canadian Cardiovascular Society class II to III angina who were on 50 mg of atenolol yet still experiencing angina symptoms were randomized to receive either placebo or nifedipine GITS 30, 60 or 90 mg/day. After four weeks of treatment, the changes in time from baseline to onset of 1 mm ST segment depression in the 183 eligible patients were 26.7+/-10.2 s, 40.9+/-11.3 s, 63.2+/-12.9 s and 70.3+/-12.6 for the placebo, and 30, 60 and 90 mg/day groups, respectively. These differences were significant (P<0.05) for the 60 and 90 mg/day groups compared with placebo and for the 60 mg/day group compared with the 30 mg/day group. The times to onset of pain and termination of exercise showed similar prolongation but did not achieve statistical significance. During the one-year open label phase of the study, patients exhibited statistically significant improvements in the time to onset of ST segment depression, time to anginal pain and time to termination of exercise at a mean dose of 52.3 mg/day of nifedipine GITS. Adverse events were primarily vasodilatory in nature. This study supports the use of nifedipine GITS in patients with chronic stable angina inadequately controlled on beta-blocker alone.
 ...
PMID:Effectiveness of nifedipine GITS in combination with atenolol in chronic stable angina. 1052 77

We examined the effects of lipopolysaccharide, a bacterial endotoxin, on synaptic plasticity in the rat hippocampal CA1 area in vitro. Lipopolysaccharide suppressed the induction of long-term potentiation elicited by tetanic stimulation and long-term depression, elicited by low-frequency stimulation of Schaffer collateral-commissural fibres at 10 and 50 microg/ml, respectively. Lipid A (1 microg/ml), the biologically active component of lipopolysaccharide, mimicked the effects of 10 microg/ml lipopolysaccharide on long-term potentiation and depression. Nifedipine, an L-type voltage-sensitive Ca(2+) channel antagonist, did not influence the induction of long-term potentiation and depression, whereas a high concentration of extracellular calcium enabled long-term potentiation induction in the presence of 10 microg/ml lipopolysaccharide. The NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV, 50 microM), nifedipine (10 microM) or lipopolysaccharide (10 or 50 microg/ml) partially reduced the magnitude of tetraethylammonium-induced long-term potentiation. Nifedipine combined with lipopolysaccharide completely blocked tetraethylammonium-induced long-term potentiation. Whole-cell voltage clamp recordings showed that lipopolysaccharide suppressed NMDA receptor-mediated excitatory postsynaptic currents (EPSCs). Our results indicate that lipopolysaccharide acutely modifies synaptic plasticity by blocking Ca(2+) entry through NMDA receptors, suggesting a possible mechanism for the amnesic action of bacterial infection.
 ...
PMID:Lipopolysaccharide inhibits induction of long-term potentiation and depression in the rat hippocampal CA1 area. 1143 Sep 15

1. Using pharmacological analysis and fura-2 spectrofluorimetry, we examined the effects of gamma-aminobutyric acid (GABA) and related substances on intracellular Ca(2+) concentration ([Ca(2+)]i) of hybrid neurones, called MD3 cells. The cell line was produced by fusion between a mouse neuroblastoma cell and a mouse dorsal root ganglion (DRG) neurone. 2. MD3 cells exhibited DRG neurone-like properties, such as immunoreactivity to microtubule-associated protein-2 and neurofilament proteins. Bath applications of capsaicin and alpha, beta-methylene adenosine triphosphate reversibly increased [Ca(2+)]i. However, repeated applications of capsaicin were much less effective. 3. Pressure applications of GABA (100 microM), (Z)-3-[(aminoiminomethyl) thio] prop-2-enoic acid sulphate (ZAPA; 100 microM), an agonist at low affinity GABA(A)-receptors, or KCl (25 mM), transiently increased [Ca(2+)]i. 4. Bath application of bicuculline (100 nM - 100 microM), but not picrotoxinin (10 - 25 microM), antagonized GABA-induced increases in [Ca(2+)]i in a concentration-dependent manner (IC(50)=9.3 microM). 5. Ca(2+)-free perfusion reversibly abolished GABA-evoked increases in [Ca(2+)]i. Nifedipine and nimodipine eliminated GABA-evoked increases in [Ca(2+)]i. These results imply GABA response dependence on extracellular Ca(2+). 6. Baclofen (500 nM - 100 microM) activation of GABA(B)-receptors reversibly attenuated KCl-induced increases in [Ca(2+)]i in a concentration-dependent manner (EC(50)=1.8 microM). 2-hydroxy-saclofen (1 - 20 microM) antagonized the baclofen-depression of the KCl-induced increase in [Ca(2+)]i. 7. In conclusion, GABA(A)-receptor activation had effects similar to depolarization by high external K(+), initiating Ca(2+) influx through high voltage-activated channels, thereby transiently elevating [Ca(2+)]i. GABA(B)-receptor activation reduced Ca(2+) influx evoked by depolarization, possibly at Ca(2+)-channel sites in MD3 cells.
 ...
PMID:Analysis of GABA(A)- and GABA(B)-receptor mediated effects on intracellular Ca(2+) in DRG hybrid neurones. 1152 1

The different mechanisms of action of beta-blockers and calcium antagonists could result in an additive therapeutic effect in patients with angina pectoris. Twenty-one male patients aged between 41 and 68 years and suffering from chronic stable angina pectoris and coronary artery disease confirmed by angiography took part in a randomized, double-blind study to examine the acute effect of 10 mg of bisoprolol, 20 mg of nifedipine, and a combination of the two drugs on hemodynamics at rest and during exercise [heart rate (HR), systolic blood pressure (SBP), rate-pressure product (RPP), cardiac index (CI), total peripheral resistance (TPR), and pulmonary capillary wedge pressure (PCP)], the behavior of the ST segment (ST), and exercise tolerance until occurrence of an ST-segment depression of 0.1 mV (W-ST01) and until onset of anginal pain (W-AP1). Following a baseline exercise test, 11 patients were given 10 mg of bisoprolol orally, whereas 10 patients received placebo. Two hours later, a second exercise test was carried out. All patients in both groups then received 20 mg of N orally. A third exercise test was performed 2 h later. On exercise, bisoprolol resulted in significant changes in HR (-16%), RPP (-22%), and CI (-16%), as well as in TPR (+ 13%); PCP was not significantly affected. Nifedipine led to significant changes in CI (+9%) and PCP (-34%). The effects of bisoprolol on HR and RPP and of nifedipine on PCP were retained in the combination. Competition was detectable as regards the opposing effects on CI and TPR. Measured by W-ST01 and ST, bisoprolol had a marked anti-ischemic effect, whereas that of nifedipine was distinctly less. There was an increase in effect after combination of the drugs (not significant). In patients with chronic angina pectoris due to coronary artery disease, bisoprolol and nifedipine had different hemodynamic profiles after acute administration; when the two drugs were combined, these effects were partly intensified and partly canceled out. There was a tendency for the effect of bisoprolol to be intensified by nifedipine in the combination. The combination of bisoprolol and nifedipine was well tolerated in the doses selected.
 ...
PMID:Hemodynamics and exercise tolerance after bisoprolol, nifedipine, and their combination in patients with angina pectoris. 1152 30

Unlike the proposed role of reactive oxygen species in neurodegeneration, acute effects of reactive oxygen on synaptic plasticity are poorly understood. Using rat hippocampal slices, we found that exposure to a high concentration (0.5-5 mm) of H(2)O(2) reduces EPSPs in both potentiated and nonpotentiated synapses. Exposure of the slices to 20 microm H(2)O(2) did not affect expression of preestablished long-term potentiation (LTP) but prevented induction of new LTP and enhanced long-term depression (LTD). Surprisingly, 1 microm H(2)O(2) caused a twofold increase in LTP compared with controls, and it further enhanced NMDA-independent LTP. A low concentration of H(2)O(2) also suppressed LTD. Nifedipine, an L-type calcium channel blocker, did not affect control LTP but blocked effects of both 1 and 20 microm H(2)O(2). Calcineurin inhibitors [FK506 (FR900506) and cyclosporin A but not rapamycin] acted similarly and also restored LTP in the presence of 20 microm H(2)O(2). These results suggest that H(2)O(2) alters NMDA-independent, voltage-gated calcium channel-mediated LTP by activating calcineurin.
 ...
PMID:Hydrogen peroxide modulation of synaptic plasticity. 1251 24

There is concern regarding the interaction of magnesium sulfate and nifedipine used concomitantly in obstetrical patients, because both are calcium channel antagonists and may induce myocardial depression as well as peripheral vasodilatation. The objective of this study was to determine the hemodynamic consequences of concomitant administration of nifedipine and magnesium sulfate in anesthetized pigs. Twelve pigs were anesthetized with sodium pentobarbital, intubated mechanically ventilated. Following placement of invasive monitors, baseline hemodynamic measurements were made. Animals were randomized to one of two groups. Group I received nifedipine first, and then magnesium sulfate. Group II received magnesium sulfate first, and then nifedipine. Hemodynamic measurements were recorded. Hypotension was treated with calcium chloride, ephedrine and phenylephrine. Nifedipine alone (Group I) decreased peripheral vascular resistance and mean arterial pressure (MAP) (P<0.05). Magnesium sulfate alone in group II decreased the first derivative of left ventricular pressure (LVdP/dt) and increased left ventricular end-diastolic pressure (LVEDP) (P<0.05). Magnesium sulfate also decreased peripheral vascular resistance and MAP The concomitant administration of nifedipine and magnesium sulfate in both groups I and 11 led to a further decrease in myocardial contractility, as evidenced by a decrease in LVdP/dt and increase in LVEDP (P<0.05). Treatment with calcium chloride or ephedrine was only partially successful in improving myocardial contractility. Phenylephrine increased peripheral vascular resistance and MAP, but did not improve myocardial function. In conclusion, the depressive effects of nifedipine and magnesium sulfate on the cardiovascular system are potentiated when administered concomitantly.
 ...
PMID:Cardiovascular consequences of the concomitant administration of nifedipine and magnesium sulfate in pigs. 1532 Nov 65

The antianginal effects of lercanidipine, a newly synthesized 1,4-dihydropyridine derivative calcium channel antagonist, were evaluated in experimental angina model rats and the effects were compared with those of nifedipine, benidipine and amlodipine. In the vasopressin-induced angina model, intravenous administration of lercanidipine dose-dependently suppressed vasopressin-induced ST-depression. Amlodipine barely suppressed it, while benidipine, at the same dose, completely suppressed it. Nifedipine had a potency between that of amlodipine and benidipine. Oral administration of lercanidipine showed similar effects to the intravenous administration test on ST change. High doses of amlodipine, benidipine and nifedipine suppressed ST-depression by almost 100%. In the methacholine-induced angina model, lercanidipine suppressed the ST elevation dose dependently. Amlodipine barely suppressed it, while benidipine at 30 microg/kg effected almost total suppression. Nifedipine had a potency between that of amlodipine and benidipine. Intraduodenal administration of lercanidipine also suppressed the ST-elevation dose dependently. Nifedipine, benidipine and amlodipine at 10 mg/kg all markedly suppressed the elevation. Lercanidipine was more potent than the other calcium channel antagonists tested. In conclusion, it was explicitly demonstrated that lercanidipine exerts potent protective effects on the ischemic electrocardiography (ECG) changes in a variety of putative angina pectoris models in rats. An antispasmolytic coronary vasodilating action may be involved in the mechanism. It is expected that lercanidipine will be useful as an antianginal agent.
 ...
PMID:Antianginal effects of lercanidipine on the vasopressin or methacholine induced anginal model in rats. 1586 84


<< Previous 1 2 3 4 5 6 7 8 9 10