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

1. Normotensive Sprague-Dawley and spontaneously hypertensive rats anaesthetized with sodium pentobarbitone were used to determine the systemic and renal actions of amlodipine, a new calcium channel blocking drug. 2. Amlodipine, 200 micrograms kg-1 plus 50 micrograms kg-1 h-1, decreased blood pressure by 12 +/- 3 mmHg in normotensive rats, although the fall was not statistically significant in the hypertensive rats; did not change renal haemodynamics and caused significant increases in urine flow, absolute and fractional sodium excretions of 70%, 91% and 113%, respectively, in normotensive rats and 65%, 91% and 96%, respectively in hypertensive rats. Fractional lithium excretion was unchanged in the normotensive rats but increased by 28% in the hypertensive animals while absolute fluid reabsorption in the proximal tubule did not change in either group. Absolute water and sodium reabsorption in the segments beyond the proximal tubule were unchanged in the normotensive rats but increased in the hypertensive animals by 24% and 22%, respectively, while fractional sodium excretion in this portion of the nephron increased by 88% and 51% in the normotensive and hypertensive rats, respectively. 3. Amlodipine, 400 micrograms kg-1 plus 100 micrograms kg-1 h-1, decreased blood pressure by 12 +/- 4 mmHg in the normotensive and by 27 +/- 5 mmHg in the hypertensive rats. Renal blood flow was not changed in either group of rats and glomerular filtration rate increased by 25% in the spontaneously hypertensive animals. There were significant increases in urine flow, absolute and fractional sodium excretions of 105%, 145% and 142%, respectively, in the normotensive rats and 224%, 421% and 259%, respectively, in the hypertensive rats. Renal blood flow was not changed in either group of rats and glomerular filtration rate increased by 25% in the spontaneously hypertensive animals. There were significant increases in urine flow, absolute and fractional sodium excretions of 105%, 145% and 142%, respectively, in the normotensive rats and 224%, 421% and 259%, respectively, in the hypertensive rats. Fractional lithium excretion was elevated by 29% and 38%, in the normotensive and hypertensive rats, respectively, but absolute fluid reabsorption at the proximal tubule remained unchanged. At the same time there were significant increases in absolute water and sodium reabsorption beyond the proximal tubule of 26% and 18%, respectively, in the normotensive animals and of 63% and 60%, respectively, in the hypertensive animals. Fractional excretion of water and sodium in the nephron regions after the proximal tubule were increased by 55% and 88%, respectively, in the normotensive rats and by 84% and 121%, respectively, in the hypertensive rats. 4. These doses of amlodipine caused modest reductions in blood pressure, minimal changes in renal haemodynamics and a natriuresis and diuresis. Proximal sodium and water reabsorption was not affected by the drug and it is suggested that the changes in tubular fluid handling were compatible with depression of reabsorption further along the tubule.
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PMID:A study of the renal actions of amlodipine in the normotensive and spontaneously hypertensive rat. 296 66

Nicardipine, a new calcium channel blocking drug of the dihydropyridine family, was administered to 63 patients at a dose of 30 or 40 mg 3 times daily in a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Nicardipine midly increased heart rate (HR) at rest and midly decreased the blood pressure (BP) at rest. When generally similar responses to the 30- and 40-mg doses were averaged, nicardipine produced a 7% increase in peak exercise HR, which was balanced by a 6% decrease in peak exercise BP. Thus, no change occurred in the exercise HR-BP product. With nicardipine, treadmill exercise duration increased 9%, time to angina increased 15%, time to 1-mm ST-segment depression increased 16%, and oxygen consumption at peak exercise increased 13%. Mean anginal frequency declined, as did mean weekly sublingual nitroglycerin consumption, but not significantly. There were more cardiovascular side effects with nicardipine than with placebo, with at least 3 patients having increased angina judged by investigators as probably related to the drug. Vasodilatory side effects were also more frequent with nicardipine, but were generally mild and well tolerated; the drug had to be discontinued in only 1 patient, because of vasodilatory effects. Nicardipine is effective and generally well tolerated in patients with chronic stable angina.
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PMID:Efficacy and safety of nicardipine for chronic, stable angina pectoris: a multicenter randomized trial. 309 55

Continuous application of transdermal nitroglycerin appears to result in tolerance to the antianginal effect. In a double-blind study the effects of continuous (24 h/day) and intermittent (16 h/day) application of transdermal nitroglycerin in a dosage of 10 mg/day were compared with the effects of placebo in 12 patients with chronic stable angina receiving treatment with beta-adrenergic blocking or calcium channel blocking agents. Exercise performance was assessed 2 to 4 hours after initial application and after 1 week of each treatment given in random order with a 3 day interval between treatments. Exercise time to onset of angina, total exercise duration and time to 1 mm ST segment depression were all significantly increased after initial application during the continuous and intermittent treatment periods. These increases were maintained after 1 week of intermittent but not continuous treatment. Thus the benefit of initial application of transdermal nitroglycerin is maintained with intermittent treatment and a daily nitrate-free interval, whereas tolerance to antianginal effect occurs with continuous treatment.
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PMID:Transdermal nitroglycerin in angina pectoris: efficacy of intermittent application. 311 51

Ryanodine was found to initially inhibit calcium uptake by cardiac sarcoplasmic reticulum. This initial depression was followed by a later marked stimulation of calcium uptake. These effects were noted when calcium uptake was measured in the presence or absence of oxalate. The requirement for preincubation with ryanodine was highly dependent on ryanodine concentration and temperature. The mechanism of action of ryanodine clearly was not an effect on oxalate entry or calcium oxalate precipitation because the effects were also observed in the absence of oxalate. Ryanodine also had no effect on passive calcium efflux from actively loaded vesicles. Because ryanodine had no effect on Ca2+-ATPase activity under defined conditions of an ATP-regenerating system and no calcium gradient, we suggest ryanodine does not change the stoichiometry of the pump. Our results are consistent with the hypothesis that ryanodine closes a calcium channel in a subpopulation of the vesicles.
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PMID:Mechanism of action of ryanodine on cardiac sarcoplasmic reticulum. 315 65

Aminoglycoside antibiotics (mmol.l-1) gentamicin (0.74), streptomycin (1.02), netilmicin (1.24), amikacin (2.23), sisomicin (2.74), dactimicin (2.75), kanamycin (3.43), kanendomycin (3.45), tobramycin (3.53) and dibekacin (4.35) produce a complete neuromuscular blockade at the isolated phrenic nerve-hemidiaphragm preparation of the rat, which is only reversed by calcium chloride. On the other hand, verapamil (2.04 mmol.l-1), a calcium channel blocker, also produces a complete neuromuscular blockade at the above preparation which is reversed by calcium chloride. Aminoglycoside antibiotics are potentially capable of interacting with verapamil and produce a complete neuromuscular blockade at concentrations significantly reduced. The neuromuscular blockade which is produced by the concurrent administration of the aminoglycoside antibiotics and verapamil is obtained with the usual therapeutic blood concentrations of the individual agents. Furthermore, the neuromuscular blockade which is produced during verapamil-aminoglycoside antibiotics interactions is completely reversed after calcium chloride administration. The mechanism by which aminoglycoside antibiotics and verapamil produce neuromuscular blockade must be the same. Both classes of drugs interfere with calcium ions movements through the calcium channels of the membrane of the motor nerve-endings inhibiting acetylcholine release at the synaptic cleft. The interaction of aminoglycoside antibiotics and calcium channel blockers is of clinical significance because when these agents are given concurrently during the perioperative period they may lead to respiratory depression or prolonged apnoea. These respiratory disturbances can be managed by slow intravenous infusion of 50 to 200 mg of calcium gluconate.
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PMID:Interaction of aminoglycoside antibiotics and calcium channel blockers at the neuromuscular junctions. 322 40

5'-N-Ethylcarboxamide adenosine (NECA) (2.2-22 nmol l-1) produced a concentration-dependent depression of both the isometric contraction and the atrial rate of the isolated, spontaneously beating guinea-pig atria. In the presence of a standard concentration of verapamil (73 nmol l-1), the dose-response curves for NECA, both for the isometric contraction and the atrial rate, were significantly shifted to the left. The inhibitory effect of NECA on the atria was almost completely reversed by the addition of calcium chloride (1.8 mmol l-1) into the organ bath. The depressive actions of NECA on the isolated atria were also antagonized by aminophylline (32 mumol l-1) and isoprenaline (24 nmol l-1). In the presence of XAC (Xanthine Amine Congener) (0.5 mumol l-1) the dose-response curve for the effect of NECA on the isometric contraction was significantly shifted to the right. In the concentration used, XAC produced no changes either in the isometric contraction or in the atrial rate. These experiments indicate that NECA may act on the adenosine A1-receptors present in the guinea-pig atria because its effects on the atria are antagonized by XAC, a more selective A1-receptor antagonist. It is concluded that NECA might act through depression of calcium channel function in the heart atria, and that the action of NECA most probably implicates A1-receptors.
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PMID:Interactions of 5'-N-ethylcarboxamide adenosine (NECA), aminophylline and dipropyl-phenyl-xanthine (XAC) on the isolated guinea-pig atria. 323 46

Increasing recognition of the importance of calcium in the pathogenesis of cardiovascular disease has stimulated research into the use of calcium channel blocking agents for treatment of a variety of cardiovascular diseases. The favorable efficacy and tolerability profiles of these agents make them attractive therapeutic modalities. Clinical applications of calcium channel blockers parallel their tissue selectivity. In contrast to verapamil and diltiazem, which are roughly equipotent in their actions on the heart and vascular smooth muscle, the dihydropyridine calcium channel blockers are a group of potent peripheral vasodilator agents that exert minimal electrophysiologic effects on cardiac nodal or conduction tissue. As the first dihydropyridine available for use in the United States, nifedipine controls angina and hypertension with minimal depression of cardiac function. Additional members of this group of calcium channel blockers have been studied for a variety of indications for which they may offer advantages over current therapy. Once or twice daily dosage possible with nitrendipine and nisoldipine offers a convenient administration schedule, which encourages patient compliance in long-term therapy of hypertension. The coronary vasodilating properties of nisoldipine have led to the investigation of this agent for use in angina. Selectivity for the cerebrovascular bed makes nimodipine potentially useful in the treatment of subarachnoid hemorrhage, migraine headache, dementia, and stroke. In general, the dihydropyridine calcium channel blockers are usually well tolerated, with headache, facial flushing, palpitations, edema, nausea, anorexia, and dizziness being the more common adverse effects.
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PMID:Differential effects of 1,4-dihydropyridine calcium channel blockers: therapeutic implications. 332 59

The effect of calcium channel blockers (Ca-antagonists) on the potency and reversibility of muscle relaxants (MR) was investigated in the in vitro phrenic nerve-hemidiaphragm and in vivo sciatic nerve-tibialis anterior preparation of rats. To increase the relevance of the experimental findings to the clinical situation, the [Ca++] and [Mg++] in vitro were the same as in the plasma of rats and humans and the stimulation parameters used in vitro and in vivo were similar to those that elicit voluntary movements of the muscles used. Both verapamil and nifedipine significantly decreased the I50 and I90 of d-tubocurarine (d-Tc), pancuronium, vecuronium, and atracurium in vitro and those of the first three MR in vivo (P less than 0.001). In vitro, the depression of the force of contraction of the diaphragm (P) caused by all the Ca-antagonist-MR combinations could be reversed only partially by washout, neostigmine, or 4-aminopyridine. In vivo, because of limitations imposed by their cardiovascular depressant effect, the muscles were exposed to lower concentrations of Ca-antagonists for shorter periods. Under these circumstances the decrease of P caused by all Ca-antagonist-MR combinations recovered spontaneously close to control levels. This study indicates that acute administration of verapamil during anesthesia may increase MR potency, but it is unlikely that spontaneous recovery or reversibility of the residual neuromuscular (NM) block at the end of anesthesia will be significantly affected. However, long-term administration of Ca-antagonists may make difficult the reversal of the residual NM block.
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PMID:Potentiation of neuromuscular blocking agents by calcium channel blockers in rats. 333 41

The effects were studied of several calcium channel blocking agents on muscle twitch, and possible interactions between these drugs and pancuronium and suxamethonium, using a rat phrenic-hemidiaphragm preparation. Nicardipine, verapamil and diltiazem each caused a concentration-related depression of muscle response. Nicardipine had the most, and diltiazem the least, potent effect. Verapamil and diltiazem 5 and 10 mumol litre-1 caused a concentration-dependent enhancement of suxamethonium-induced neuromuscular blockade, but increased the effect of pancuronium only at 10 mumol litre-1. Nicardipine 10 mumol litre-1 significantly enhanced pancuronium-induced neuromuscular blockade, but not that produced by suxamethonium.
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PMID:Differential effects of calcium channel blocking agents on pancuronium- and suxamethonium-induced neuromuscular blockade. 337 24

Our previous study demonstrated that class I antiarrhythmics (fast sodium channel blockers) increased sinoatrial conduction time (SACT) in a dose-related fashion, indicating that a fast sodium current might play an important role in sinoatrial conduction. To assess a role of a slow calcium current in sinoatrial conduction, we examined effects of calcium channel blockers (diltiazem, verapamil, AQ-A 39, dilazep and bepridil) on SACT estimated by the constant atrial pacing in addition to on sinus cycle length (SCL) and on atrial developed tension (DT), using the isolated and blood-perfused dog right atrium. These calcium entry blockers except for bepridil were administered into the cannulated sinus node artery at an infusion rate of 0.2, 0.4 and 1.0 micrograms/min and bepridil at a rate of 0.6, 1.2 and 3.0 micrograms/min. The calcium antagonistic agents produced a dose-dependent decrease in DT and increase in SCL. The observed order of depression of inotropism was verapamil greater than diltiazem greater than bepridil = dilazep greater than AQ-A 39, while the order of negative chronotropism was diltiazem greater than verapamil greater than AQ-A 39 greater than dilazep greater than bepridil. However, as to dromotropism none of the five drugs exerted significant influences on SACT. From the previous and present results it is concluded that the fast sodium current may be predominantly important in sinoatrial conduction.
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PMID:Effects of calcium channel blockers on sinoatrial conduction in the isolated and blood-perfused dog atrium. 348 62


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