UMLS:C0011570 - FACTA Search

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)

The effects of drugs were evaluated in 47 cases with variant angina (VA), 19 with resting angina showing ST depression (RA), and 84 with unstable angina (UA). In VA patients, calcium antagonists were effective in 87.1% of the cases, while other drugs were effective in 56.3%. The difference was statistically significant. In RA patients, calcium antagonists were effective in 80.0% of the cases and other drugs in 44.4%. Nifedipine was effective in all 5 cases with coronary stenosis of more than 75.0%. All cases of RA had multiple vessel disease and nifedipine was effective in 80.0% of the patients. Nifedipine was effective in 83.3% of VA cases showing ST elevation during an exercise test, and was particularly effective in all patients having attacks only at rest. The effects of nifedipine were confirmed in 83.3% of UA cases. These results indicate that calcium antagonists are effective in VA, RA, and UA.
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PMID:Effects of calcium antagonists, especially nifedipine, on variant angina, resting angina, and unstable angina. 716 75

Nifedipine acts on smooth muscle cells to prevent the influx of calcium ions. The present study was undertaken to see whether a relaxatory effect of nifedipine is present on esophageal smooth muscle as well as on vascular smooth muscle. The experiment was performed on anesthetized dog's lower esophageal sphincter pressure (LESP). Nifedipine (0.5 mg/kg) administered sublingually caused rapid and marked depression of LESP. LESP response to either ACO-tetragastrin (0.5 microgram/kg) or bethanechol (5 microgram/kg) was inhibited partially but markedly. This inhibition might be caused by prevention of calcium-ion influx. This depressant effect of nifedipine on LESP both in resting state and in stimulated state is able to apply to therapy of hypermotile disorders of the esophagus.
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PMID:[Effect of nifedipine on canine LESP (author's transl)]. 732 57

The effectiveness of nifedipine in treating angina pectoris at rest was evaluated in 14 patients with frequent ischemic episodes associated with S-T segment elevation or depression. The trial consisted of (1) a 48 hour control period; (2) a placebo period and a period of treatment with nifedipine of 48 hours each; and (3) a second placebo period and a second period of treatment with nifedipine of 24 hours each. The efficacy of treatment was evaluated by continuous electrocardiographic recording to detect painless ischemic episodes. During coronary angiography coronary spasm was demonstrated in five patients. The ergonovine maleate test was positive in seven of eight patients. No statistically significant difference was found in the mean daily number of ischemic episodes between the control period and the first placebo period, or between the control and the second placebo periods. Nifedipine produced a highly significant reduction in the mean daily number of episodes compared with the response to placebo during the first as well as the second period. Nifedipine is effective in angina at rest caused by coronary arterial spasm. The prevention of ischemia may be related to the ability of nifedipine to decrease calcium-dependent coronary muscle tone and to prevent coronary spasm.
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PMID:Treatment of angina at rest with nifedipine: a short-term controlled study. 736 74

1. The aim of this study was the pharmacological characterization of tachykinin NK1 and NK2 receptors mediating contraction in the circular muscle of the guinea-pig ileum and proximal colon. The action of substance P (SP), neurokinin A (NKA) and of the synthetic agonists [Sar9]SP sulphone, [Glp6,Pro9]SP(6-11) (septide) and [beta Ala8]NKA(4-10) was investigated. The affinities of various peptide and nonpeptide antagonists for the NK1 and NK2 receptor was estimated by use of receptor selective agonists. 2. The natural agonists, SP and NKA, produced concentration-dependent contraction in both preparations. EC50 values were 100 pM and 5 nM for SP, 1.2 nM and 19 nM for NKA in the ileum and colon, respectively. The action of SP and NKA was not significantly modified by peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each). 3. Synthetic NK1 and NK2 receptor agonists produced concentration-dependent contraction of the circular muscle of the ileum and proximal colon. EC50 values were 83 pM, 36 pM and 10 nM in the ileum, 8 nM, 0.7 nM and 12 nM in the colon for [Sar9]SP sulphone, septide and [beta Ala8]NKA-(4-10), respectively. The pseudopeptide derivative of NKA(4-10), MDL 28,564 behaved as a full or near-to-full agonist in both preparations, its EC50s being 474 nM and 55 nM in the ileum and colon, respectively. 4. Nifedipine (1 microM) abolished the response to septide and [Sar9]SP sulphone in the ileum and produced a rightward shift and large depression of the response in the colon. The response to [beta Ala8]NKA(4-10) was abolished in the ileum and largely unaffected in the colon. 5. The NK1 receptor antagonists, (+/-)-CP 96,34, FK 888 and GR 82,334 competitively antagonized the response to septide and [Sar9]SP sulphone in both preparations without affecting that to [beta Ala8]NKA(4-10). In general, the NK1 receptor antagonists were significantly more potent toward septide than [Sar9]SP sulphone in both preparations. 6. The NK2 receptor antagonists, GR 94,800 and SR 48,968 selectively antagonized the response to [beta Ala8]NKA(4-10) without affecting that to [Sar9]SP sulphone or septide in the ileum and colon. SR 48,968 produced noncompetitive antagonism of the response to the NK2 receptor agonist in the ileum and competitive antagonism in the colon. 7. MEN 10,376 and the cyclic pseudopeptide MEN 10,573 antagonized in a competitive manner the response to [beta Ala8]NKA(4-10) in the ileum and colon. While MEN 10,573 was equipotent in both preparations, MEN 10,376 was significantly more potent in the colon than in the ileum. MEN 10,376was also effective against septide in both preparations, without affecting the response to [Sar9] SP sulphone. MEN 10,573 antagonized the response to [Sar9]SP sulphone and septide in both preparations,pKB values against septide being intermediate, and significantly different from, those measured against[Beta Ala 8]NKA(4-10) and [Sa9]lSP sulphone.8. These findings show that tachykinin NK1 and NK2 receptors mediate contraction of the circular muscle of the guinea-pig ileum and colon. In both preparations NK1 receptor antagonists display higher apparent affinity when tested against septide than [Sar9]SP sulphone. These findings are compatible with the proposed existence of NK1 receptor subtypes in guinea-pig, although alternative explanations (e.g.agonist binding to different epitopes of the same receptor protein) cannot be excluded at present.Furthermore, an intraspecies heterogeneity of the NK2 receptor in the circular muscle of the guinea-pig ileum and colon is suggested.
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PMID:Comparison of tachykinin NK1 and NK2 receptors in the circular muscle of the guinea-pig ileum and proximal colon. 751 2

We studied the effects of 6-week treatment with nifedipine (35 mg/kg/day orally, p.o.) on streptozotocin (STZ)-induced diabetic rats. Injection of STZ [45 mg/kg intravenously, (i.v.) single dose] produced a significant increase in blood pressure (BP), bradycardia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypothyroidism, depression in left ventricular developed pressure (LVDP), cardiomyopathy, and nephropathy. Treatment of diabetic rats with nifedipine normalized the BP and prevented bradycardia. Insulin levels were decreased after nifedipine treatment in diabetic as well as nondiabetic rats. However, serum glucose levels were also partially decreased in diabetic animals by nifedipine treatment. In control animals as well, glucose levels were in the normal range despite lower insulin levels observed after nifedipine treatment. Nifedipine treatment significantly prevented STZ-induced increase in cholesterol and triglyceride levels. Nifedipine treatment significantly prevented STZ-induced hypothyroidism and also prevented STZ-induced cardiac depression and cardiomyopathy. Our data indicate that nifedipine increases insulin sensitivity and has some beneficial effects on cardiovascular parameters. It may therefore be considered a preferred drug in the treatment of hypertension associated with diabetes mellitus.
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PMID:Effects of chronic nifedipine treatment on streptozotocin-induced diabetic rats. 756 66

We wished to determine if drugs with negative inotropic properties would exacerbate the transient myocardial depression associated with intravenous (i.v.) cocaine administration. The influence of propranolol, nifedipine, or verapamil pretreatment on the myocardial depressant effect of cocaine was examined in 13 chronically instrumented, conscious dogs. Cocaine alone (4 mg/kg i.v.) caused significant increases in heart rate (HR), mean arterial pressure (MAP), and rate-pressure product (RPP), effects consistent with sympathetic stimulation. Regional ejection fraction (EF) (determined by two-dimensional echocardiography), however, decreased from 56 +/- 5% (mean +/- SE) at baseline to 34 +/- 6% at 1 min and to 41 +/- 5% at 2 min after cocaine administration but recovered to 49 +/- 4% at 10 min. Pretreatment with propranolol (0.5 mg/kg i.v.) blunted the rate-pressure response to cocaine by 28%. Regional EF decreased from 53 +/- 5% at baseline to 26 +/- 3% (p < 0.01 as compared with cocaine alone) at 2 min after cocaine and was still reduced at 33 +/- 3% (p < 0.001 as compared with cocaine alone) at 10 min. Pretreatment with verapamil (10 mg i.v. 10 min before cocaine) blunted the rate-pressure response very little, but regional left ventricular (LV) EF decreased less, from 58 +/- 3% to only 46 +/- 5% at 2 min, and was almost normal at 10 min (57 +/- 5%). Nifedipine [90 mg sustained-release orally (p.o.) administered 5 h earlier] also reduced the myocardial depressant effect of cocaine at 2 min [regional EF decreased from 50 +/- 2% at baseline to 38 +/- 4% (cocaine alone), 56 +/- 3 to 49 +/- 4% (nifedipine and cocaine), p < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of propranolol, verapamil, and nifedipine on the myocardial depressant effect of cocaine. 759 26

We have studied vertical synaptic pathways in two cytoarchitectonically distinct areas of rat neocortex--the granular primary somatosensory (SI) area and the agranular primary motor (MI) area--and tested their propensity to generate long-term potentiation (LTP), long-term depression (LTD), and related forms of synaptic plasticity. Extracellular and intracellular responses were recorded in layer II/III of slices in vitro while stimulating in middle cortical layers (in or around layer IV). Under control conditions, 5 Hz theta-burst stimulation produced LTP in the granular area, but not in the agranular area. Agranular cortex did generate short-term potentiation that decayed within 20 min. Varying the inter-burst frequency from 2 Hz to 10 Hz reliably yielded LTP of 21-34% above control levels in granular cortex, but no lasting changes were induced in agranular cortex. However, the agranular cortex was capable of generating LTP if a GABAA receptor antagonist was applied locally at the recording site during the induction phase. In contrast to LTP, an identical form of homosynaptic LTD could be induced in both granular and agranular areas by applying low frequency stimulation (1 Hz for 15 min) to the middle layers. Under control conditions, both LTP and LTD were synapse-specific; theta-burst or low-frequency stimulation in the vertical pathway did not induce changes in responses to stimulation of a layer II/III horizontal pathway. Application of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (AP5) blocked the induction of both LTP and LTD in granular and agranular cortex. In the presence of AP5, low-frequency conditioning stimuli yielded a short-term depression in both areas that decayed within 10-15 min. Nifedipine, which blocks L-type, voltage-sensitive calcium channels, slightly depressed the magnitudes of LTP and LTD but did not abolish them. Synaptic responses evoked during theta-burst stimulation were strikingly different in granular and agranular areas. Responses in granular cortex were progressively facilitated during each sequence of 10 theta-bursts, and from sequence-to-sequence; in contrast, responses in agranular cortex were stable during an entire theta-burst tetanus. The results suggest that vertical pathways in primary somatosensory cortex and primary motor cortex express several forms of synaptic plasticity. They were equally capable of generating LTD, but the pathways in somatosensory cortex much more reliably generated LTP, unless inhibition was reduced. LTP may be more easily produced in sensory cortex because of the pronounced synaptic facilitation that occurs there during repetitive stimulation of the induction phase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Different forms of synaptic plasticity in somatosensory and motor areas of the neocortex. 762 55

The antianginal effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in various experimental angina models and compared with those of nifedipine and propranolol. In anesthetized dogs, YM-16151-4 (0.3 and 1 mg/kg intravenously, i.v.) increased coronary blood flow and reduced myocardial oxygen consumption (MVO2). In isolated dog coronary arteries, YM-16151-4 concentration-dependently inhibited 3,4-diaminopyridine-induced rhythmic contractions with an IC50 value of 91 nM. In anesthetized rats, YM-16151-4 also inhibited the ST-segment depression induced by vasopressin (0.5 U/kg i.v.) with an ED50 value of 29 mg/kg orally, (p.o.). Nifedipine was also effective in these models, but propranolol was not. In addition, YM-16151-4 (0.3 mg/kg i.v.) inhibited the ST-segment elevation in the epicardial ECG induced by coronary artery occlusion in anesthetized dogs. Propranolol (1 mg/kg i.v.) also inhibited this elevation, but nifedipine (0.003 mg/kg i.v.) did not. In anesthetized dogs, furthermore, the prolongation of PQ-interval induced by YM-16151-4 was almost the same as that induced by propranolol. These results demonstrate that YM-16151-4, in contrast to nifedipine and propranolol, is fully effective in these various types of angina models. Thus, YM-16151-4 is expected to prove a valuable antianginal agent in treatment of various types of angina pectoris, with these antianginal effects resulting from the sum of its calcium entry blocking and beta 1-adrenoceptor blocking activities.
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PMID:Antianginal effects of YM-16151-4 in various experimental angina models. 768 38

Extracellular and intracellular recordings were obtained from striatal neurons in a brain slice preparation in order to characterize the post-receptor mechanisms underlying striatal posttetanic long-term depression (LTD). Striatal LTD was blocked in neurons intracellularly recorded either with 1,2-bis (o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) or with EGTA, calcium (Ca2+) chelators. Intracellular injection of QX-314, a lidocaine derivative that has been shown to block voltage-dependent sodium channels, abolished action potential discharge and blocked striatal LTD. However, under this condition, striatal LTD was restored when, immediately before the delivery of the tetanus, the cell was depolarized at a membrane potential ranging between -30 mV and -20 mV by injecting continuous positive current. Nifedipine (10 microM), a blocker of voltage-dependent L-type Ca2+ channels, blocked striatal LTD. Nifedipine by itself altered neither cortically evoked EPSPs nor input resistance and firing properties of most of the recorded cells. Striatal LTD was also reduced or blocked by incubation of the slices in the presence of the following inhibitors of Ca(2+)-dependent protein kinases: staurosporine (10-50 nM), 1-(5-isoquinolinesulfonyl)-2- methylpiperazine (H-7; 10-50 microM), and calphostin C (1 microM). Our findings suggest that generation of striatal LTD requires a Ca2+ influx through voltage-dependent nifedipine-sensitive Ca2+ channels and a sufficient intracellular free Ca2+ concentration. Furthermore, this form of synaptic plasticity seems to involve the activation of Ca(2+)-dependent protein kinases. Different drugs, acting at receptor and/or post-receptor level, may affect this form of synaptic plasticity and might alter the formation of motor memory.
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PMID:Post-receptor mechanisms underlying striatal long-term depression. 804 57

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

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