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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organic calcium (Ca++) channel antagonists enhance opiate-induced analgesia and antagonize respiratory depression produced by morphine in rodents. Our preliminary data indicated that verapamil reduces the subjective effects of morphine in humans. We therefore assessed morphine-verapamil interactions in 12 experienced, male polydrug users with histories of heroin abuse by using a double-blind, cross-over study design. Treatments consisted of two drug infusions. Either verapamil, 2.5 or 10 mg, or saline was infused, 30 ml i.v. over 2 min; half way through this infusion either 10 mg of morphine or saline was infused, 3 ml i.v. over 10 sec, via a second catheter. Autonomic parameters, responsiveness to pain and subjective self-reports of mood and feeling state were measured over 4 hr. Analgesia was measured using a finger pressure test and hand immersion in ice water. Respiration was measured by using respiratory inductive plethysmography and transcutaneous CO2 levels. The Addiction Research Center Inventory (ARCI) was used to measure the subjective effects. Morphine had a liminal effect on pain threshold, but verapamil potentiated this effect to elevate pain threshold significantly. Verapamil did not affect the ability of morphine to increase pain endurance or to produce respiratory depression. Morphine produced positive affective responses, as demonstrated by elevated scores on the Morphine-Benzedrine Group subscale of the ARCI. Verapamil alone produced no effects on any ARCI subscales; however, 10 mg of verapamil significantly reduced morphine-elevated MBG scores over a 3-hr period. The results suggest the euphorigenic and analgesic effects of opioids may be differentiated by using Ca++ channel blockers.
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PMID:Effects of verapamil on morphine-induced euphoria, analgesia and respiratory depression in humans. 826

Verapamil can produce depression of left ventricular function, delayed atrioventricular conduction, and hypotension, which can be potentiated by hyperkalemia. We sought to investigate a direct cardiac interaction between verapamil and hyperkalemia. Studies utilized isolated guinea pig hearts (Langendorff) paced at 250 beats/min. Hearts were randomly assigned to perfusion (Krebs-Henseleit buffer) with potassium concentrations ([K]+) of 1.5, 3, 6 and 9 mmol/l. Infusion of verapamil at rates of 0.2 to 60 micrograms/min (approximately 3 x 10(-8) to 10(-5) mol/l) produced concentration-dependent reduction of isovolumic left ventricular developed pressure. As [K]+ increased, concentration response curves showed parallel shifts to the left. The ED50 for reduction of left ventricular developed pressure significantly decreased: 8.2 +/- 3.7, 2.9 +/- 1.4, 1.2 +/- 0.7, 0.6 +/- 0.2 micrograms/min (mean +/- SD), respectively. Nifedipine and diltiazem were also studied in hearts perfused with 3 and 9 nmol/l [K]+. Infusion of nifedipine 0.003-1 microgram/min (approximately 10(-9) to 3 x 10(-7) mol/l) produced concentration-dependent reduction of left ventricular developed pressure but the ED50 was not affected by [K]+: 0.06 +/- 0.03 and 0.05 +/- 0.04 microgram/min, respectively. Nifedipine vehicle was without effect at the infusion rates tested. Infusion of diltiazem 2-200 micrograms/min (approximately 3 x 10(-7) to 3 x 10(-5) mol/l) also produced concentration-dependent reduction of left ventricular developed pressure. The ED50 for diltiazem-induced reduction of left ventricular developed pressure was significantly reduced by elevated [K]+: 20.1 +/- 6.7 and 3.5 +/- 0.9 micrograms/min with 3 and 9 mmol/l [K]+, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of hyperkalemia on myocardial depression by verapamil in isolated hearts. 826 19

Our study evaluated the effects of verapamil in elderly patients with stable effort angina using a medium-term double-blind placebo-controlled protocol. Thirty-nine consecutive patients, 23 middle-age patients (50 +/- 6 years; range 38-60 years) and 16 elderly patients (66 +/- 2 years; range 65-70 years) with exertional angina were chosen. After a run-in period, both groups received treatment with either placebo or verapamil--360 mg daily--for 4 weeks. During treatment, weekly angina frequency and nitroglycerin consumption were significantly reduced in both groups. Verapamil significantly decreased the rate-pressure product at rest in elderly patients and in both groups at submaximal exercise, due to a reduction in heart rate in both groups and to a more marked decrease in arterial pressure in older patients. At peak exercise, the rate-pressure product was unchanged in both groups after verapamil, while exercise capacity showed a significant improvement in the middle-aged, and ST segment depression was reduced in both groups. After verapamil, 30% of middle-aged patients and 44% of elderly patients had to stop exercising because of angina. Side effects were rare and no drop-out was recorded. Verapamil exerted its antianginal action by means of a decrease in myocardial oxygen consumption at rest and at submaximal exercise in the elderly, while only at submaximal exercise in the middle-aged. Therefore verapamil at the dose of 360 mg daily proved an effective antianginal drug with a safe effect profile also in elderly patients.
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PMID:Age-related changes of antianginal effects of verapamil in patients with stable effort angina. A medium term randomized double-blind placebo controlled trial. 833 70

Adenosine versus Verapamil and other Antiarrhythmic Drugs: Paroxysmal supraventricular tachycardia is the most common sustained arrhythmia during pregnancy. Verapamil has been the most commonly used agent for the treatment of PSVT with a narrow QRS complex. Potential side effects of verapamil including systemic hypotension, acute heart failure, bradyarrhythmia and heart block may occur in pregnant women; after placental transfer bradycardia, heart block, depression of contractility and hypotension may be induced in the fetus. We report on the case of a 22-year old pregnant woman with hypotension and tachycardia, who was admitted for suspected haemorhagic shock. Indeed, she suffered from paroxysmal supraventricular tachycardia, which was successfully terminated by intravenous adenosine. Because of its known rapid onset, high effectivity, low incidence and brevity of side effects in the mother and comparative safety in the fetus, adenosine seems to be the drug of choice for treating PSVT during pregnancy.
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PMID:[Paroxysmal supraventricular tachycardia in pregnancy. Value of adenosine and other anti-arrhythmia agents]. 876 89

The effects of two calcium channel blockers (verapamil and nicardipine) on indirectly elicited muscle twitch and possible interactions between these drugs and non-depolarising muscle relaxants (vecuronium, atracurium, pancuronium) were investigated using isolated rat phrenic nerve-hemidiaphragm preparations. Both verapamil 10(-5) M and nicardipine 10(-6) M caused significant depression of twitch amplitude. Verapamil significantly increased vecuronium- and atracurium-induced neuromuscular block, but not that produced by pancuronium. Nicardipine potentiated atracurium-induced neuromuscular block but had no effect on pancuronium- and vecuronium-induced twitch depression. Neostigmine 10(-6) M did not produce any significant changes in the maximal recovery of twitch depression induced with calcium channel blockers and muscle relaxants combinations; also, neostigmine had no effect on maximal recovery time of twitch depression.
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PMID:Interactions of calcium channel blockers with non-depolarising muscle relaxants in vitro. 877 69

The wide use of ABPM has resulted in greater appreciation of the circadian time structure of BP variability and its clinical relevance. It is now recognized that the day-night change in BP results from an interplay of circadian rhythms in neurohumoral mechanisms coupled with temporal patterns in physical activity and mental load. The composite effect and balance of these endogenous and exogenous cyclic phenomena give rise to elevated BP during diurnal activity and reduced BP during nighttime repose in both normotension and uncomplicated essential hypertension. The balance is frequently disturbed in complicated and secondary forms of hypertension causing gross alteration of the 24-hour BP profile. ABPM also reveals the efficiency of antihypertensive treatment throughout the 24 hours and as a function of drug administration time. The pharmacokinetics and/or pharmacodynamics of antihypertensive medications have been demonstrated to vary with ingestion time. Such time-dependencies arise from circadian rhythms in BP and underlying mechanisms. The effect of antihypertensive medications is not simply superimposed upon endogenous bioperiodicities. Rhythms in neurohumoral mechanisms of BP control may modulate treatment effect. Certain aspects of the shape of the 24-hour BP profile, such as the magnitude of the morning surge and nocturnal decrease, have been implicated as determinants of morbid and mortal cardiovascular events. One large clinical multicenter investigation, known as the CONVINCE (Controlled Onset Verapamil Investigation of Clinical Endpoints) trial, is aimed at assessing the impact (cardiovascular morbidity and mortality) of verapamil chronotherapy over standard diuretic or beta anatagonist treatment in hypertensive patients with at least one risk factor of coronary heart disease. ABPM will help ascertain to what extent depression of the morning surge in BP relates to reduction in cardiac morbidity and mortality in this as well as other such trials. In any event, the importance of ABPM and the indices derived from its application are just beginning to be appreciated and explored.
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PMID:Ambulatory blood pressure monitoring. Application to clinical medicine and antihypertension medication trials. 885 50

Verapamil produces comparatively greater in vivo left ventricular (LV) depression than other calcium channel antagonists produce, possibly because of myocardial metabolic derangements in addition to L-channel antagonism. Therefore, we studied myocardial lipid and carbohydrate usage and the effect of insulin treatment during progressive verapamil toxicity. Verapamil was infused through the portal vein to simulate oral overdose. Eighteen mongrel dogs were instrumented to measure multiple hemodynamic and metabolic parameters. After 1-week recovery, dogs underwent control euglycemic insulin dose-response studies (n = 6) in the conscious state: at 1,000 mU/mm insulin infusion rate, myocardial glucose and lactate extraction increased seven- and threefold, respectively with no change in coronary artery blood flow or ventricular elasticity and end-systole (Ees). In 12 separate dogs, intraportal graded verapamil toxicity was induced in 3 h by increasing the infusion rate hourly: 0.04 -- 0.08 -- 0.1 mg/kg/mm. At the end of hour 3, myocardial extraction of free fatty acids decreased from 33 +/- 4 to 9 +/- 3% (mean +/- SEM, p < 0.05), without significant change in myocardial blood flow or arterial free fatty acid concentration. Verapamil toxicity increased arterial glucose from 3.5 +/- 0.16 to 6.1 +/- 1.1 mM; simultaneously, myocardial glucose extraction doubled, although endogenous insulin concentrations did not increase. Arterial lactate concentrations and net myocardial lactate uptake both increased (p < 0.05 vs basal blue). Ees decreased from 28 +/- 1 mm Hg/mm (basal) to 20 +/- 2 mm Hg/mm (end of hour 3, p <0.05). Animals were randomized into two treatment groups; either (a) insulin-glucose (1,000 mU/mm, n 6; arterial glucose was clamped +/- 10% with 50% dextrose), or (b) saline controls (n = 6) that received equivalent volume of saline. After 1-h insulin treatment, Ees increased to 34 + 3 mm Hg; in controls, Ees was 15 +/- 3 mm Hg/mm (p < 0.05). With insulin-glucose treatment, neither myocardial glucose nor lactate extraction increased significantly (p = 0.06 for lactate). Verapamil therefore inhibits myocardial fatty acid uptake and impedes insulin-stimulated myocardial glucose uptake; under these conditions, insulin-glucose treatment increases myocardial contractile function independent of increased sugar transport. These findings indicate that verapamil toxicity produces myocardial insulin resistance and, potentially, nutrient deprivation that may contribute to clinically relevant negative inotropy.
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PMID:Myocardial metabolism during graded intraportal verapamil infusion in awake dogs. 885 43

1. We measured the ability of glucagon and amrinone, used alone and in combination, to improve the myocardial function in a rat isolated heart model of calcium channel blocker (CCB) cardiotoxicity. 2. Verapamil 10(-4) mol consistently decreased heart rate and cardiac contractile force in our Langendorff rat isolated heart preparations. Glucagon increased the heart rate in a dose-dependent fashion. Amrinone increased the heart rate only at the 1 x 10(-1) mol concentration, and had no significant effect on cardiac contractility. 3. A positive linear correlation was found between the glucagon concentration and the percent recovery of baseline contractile force. 4. Although complete reversal of verapamil-induced myocardial depression occurred at glucagon concentrations of > 3 x 10(-6) mol, amrinone produced only 23.8 +/- 3.6% recovery from baseline at its highest concentration (4 x 10(-3) mol). 5. When glucagon and amrinone were administered together, there was no additional increase over glucagon alone in the increase in contractile force. 6. Glucagon, and not amrinone, is an appropriate agent, capable of reversing verapamil-induced myocardial toxicity in this rat isolated heart model. In vivo studies should be performed to assess whether this may be a reliable therapy in clinical cases.
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PMID:The effects of amrinone and glucagon on verapamil-induced myocardial depression in a rat isolated heart model. 918 18

It is well known that disturbance of calcium homeostasis has a significant role in the development of neurodegenerative disorders, such as Alzheimer's disease (AD). Our recent data suggest that acute treatment with the calcium antagonist verapamil can improve some behavioral deficits in an experimental model of AD. Therefore, the present study was done to establish the effect of chronically administered verapamil on cognitive and noncognitive behavior of rats with bilateral electrolitical lesions of nucleus basalis manocellularis (NBM)--an animal model of AD. The NBM lesions produce a deficit in performance of diverse behavior tests: active avoidance (AA), low level of fear (the open field test) as well as aggressive (the test of foot-shock induced aggression) and depressive (the learned helplessness test) behavior. Verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg i.p.) or saline solution (1 ml/kg i.p.) were injected 24 hr after the lesion of NBM and then repeatedly administered during the next 8 days (twice a day). Performance of the two-way active avoidance test, the open field test, the foot shock-induced aggression test and the learned helplessness test were done on day 4 after the last verapamil or saline treatment (day 13 after the lesion). Verapamil in doses of 2.5 and 5.0 mg/kg significantly ameliorated the deficit in the performance of AA, the open field behavior, and the depression, but not the aggressive behavior. The obtained beneficial effect of chronic administered verapamil suggests that the regulation of calcium homeostasis during the early period after NBM lesions might be a reasonable way to prevent the behavioral deficits in an experimental model of AD.
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PMID:Neuroprotective effect of chronic verapamil treatment on cognitive and noncognitive deficits in an experimental Alzheimer's disease in rats. 952 58

Effects of ketamine on the sodium (INa) and L-type calcium currents (ICa) were examined by using whole-cell patch clamp techniques in guinea pig single ventricular myocytes. The mode of action of ketamine was compared with those of quinidine, a sodium channel blocker, and verapamil, a calcium channel blocker. Ketamine (30-300 microM) inhibited both INa and ICa in a concentration-dependent manner. Quinidine (30 microM) and verapamil (0.1 microM) produced use-dependent depression of INa and ICa, respectively. The amplitude of INa elicited by the first depolarizing pulse after a long quiescent period was slightly decreased by quinidine. During a train of depolarizing pulse the current amplitude decreased gradually, and reached a steady state level in the quinidine-treated cell (use-dependent block, UDB). Verapamil produced a similar mode of inhibition of ICa, i.e., UDB. In contrast, ketamine produced significant decrease in INa and ICa elicited by the first depolarizing pulses and the decreases of both currents were not augmented during a train of depolarizing pulses. From these results, it can be concluded that ketamine produces tonic block of the cardiac sodium and calcium channels and the mode of inhibition is clearly different from UDB by quinidine and verapamil.
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PMID:Tonic block of the sodium and calcium currents by ketamine in isolated guinea pig ventricular myocytes. 959 21


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