Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MCI-154 is a potent nonglycoside and non-sympathomimetic cardiotonic agent with a pyridazinone structure. We assessed its cardiac and coronary vasodilator effects by use of isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. The drug (1-100 nmol) was injected intraarterially. MCI-154 increased the force of contraction of paced and unpaced papillary muscles but failed to affect the rate of automaticity of the latter. It increased sinus rate and shortened AV conduction time by accelerating AV nodal conduction, but in all doses examined it produced no arrhythmias. In all preparations, it increased blood flow. All the effects were long-lasting (1-2 h). MCI-154, however, was not homogeneously effective on these cardiovascular variables. The drug was nearly equieffective in producing a positive inotropic effect and coronary vasodilatation, but less effective in producing positive chronotropic and dromotropic effects. In having such a cardiovascular profile, MCI-154 most resembles milrinone among new cardiotonic agents, although unlike milrinone, its main mechanism of cardiotonic action is believed to be the sensitization of the contractile proteins to Ca2+. Whatever mechanisms are involved, the revealed cardiovascular profile of MCI-154 justifies its clinical trial in the treatment of heart failure.
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PMID:Cardiac and coronary vasodilator effects of the novel cardiotonic agent, MCI-154, assessed in isolated, blood-perfused dog heart preparations. 245 Feb 40

Betaxolol is a new cardioselective beta-blocker without any intrinsic sympathomimetic activity. A study of the cardiac electrophysiological effects of this molecule used intravenously was carried out in 20 patients. Betaxolol prolongs the sinus cycle (+ 25%, p 0.001), prolongs the sino-atrial conduction time (+ 20.1%) and atrio-hissian conduction time (+ 10.8%, p 0.001), and prolongs the refractory periods at all levels: atrial (+ 8%), nodal (+ 20.8%), right ventricular (+ 4.3%). These findings confirm the electrophysiological characteristic effects of the beta-blockers series; however, the moderate but significant increase of the refractory ventricular period, seems to provide this molecule with a certain degree of originality in this therapeutic class.
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PMID:[Study of electrophysiological effects of betaxolol]. 288 23

The authors examined and compared the direct effects of three volatile anesthetic agents and three sympathomimetic agonists on transmembrane action potential (AP) characteristics and automaticity of sinoatrial (SA) nodal pacemaker cells. SA nodal tissue was isolated from guinea pig hearts and suffused in vitro with oxygenated Krebs-Ringer solution. Electrophysiologic variables measured were: amplitude of the AP, slopes of phase 4 and of phase 0 of the AP, AP duration, and spontaneous sinus rate. The authors found that 1 and 2 MAC equivalents of each anesthetic, 0.8 and 1.6 vol % halothane, 1.4 and 2.8 vol % isoflurane, and 1.7 and 3.4 vol % enflurane similarly depressed the slopes of phase 4 and 0 of the AP, prolonged AP duration, and slowed the sinus rate at 1 and 2 MAC equivalents. Isoproterenol, 0.25 microM, and epinephrine, 50 microM, maximally enhanced the slopes of phase 4 and 0 of the AP, shortened AP duration, and increased the sinus rate, but phenylephrine, 50 microM, only moderately increased the slope of phase 4 and the sinus rate. Each of the three anesthetics caused baseline depressions of phase 4 and phase 0 slopes and of automaticity of SA nodal cells; the fall in sinus rate was counteracted, but was not reversed maximally by increasing the concentrations of isoproterenol, epinephrine, or phenylephrine. Regression analyses of linearly transformed data showed that each of the anesthetics similarly depressed basal sinus rate, so that changes in rate produced with isoproterenol and epinephrine were not different from those observed with beta agonists in the absence of anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Volatile anesthetics attenuate sympathomimetic actions on the guinea pig SA node. 289 8

1 Atrio-ventricular conduction and its modifications induced by six beta-adrenoceptor blocking agents and isoprenaline have been investigated in the anaesthetized dog using the extrastimulus technique and measuring atrial (AERP), nodal (NERP), global (GERP) effective refractory periods as well as global functional refractory period (GFRP). 2 When beta-adrenoceptor blockade was produced by (+/-)-propranolol (beta 1 + beta 2-adrenoceptor blockade) which is devoid of intrinsic sympathomimetic activity (ISA) but has membrane stabilizing effects (MSE), sotalol (beta 1 + beta 2-adrenoceptor blockade, no ISA, no MSE) and atenolol (beta 1-adrenoceptor blockade, no ISA, no MSE), all parameters were significantly increased. When beta-adrenoceptor blockade was achieved with pindolol (beta 1 + beta 2-adrenoceptor blockade) and practolol (beta 1-adrenoceptor blockade) which have ISA but no MSE, all parameters remained unchanged, as was also the case with (+)-propranolol, which has MSE but neither ISA nor beta-adrenolytic properties. 3 Isoprenaline at high doses significantly reduced the refractory periods but when infusion was stopped, marked but reversible conduction depression was observed. 4 It thus appears that beta-adrenoceptor blockade but not MSE is responsible for the onset of atrial and AV-conduction impairment and that ISA affords protection against this impairment.
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PMID:Beta-adrenoceptor blockade and atrio-ventricular conduction in dogs. Role of intrinsic sympathomimetic activity. 612 66

1 In 46 patients (16 female and 30 male), aged between 18 and 73 years and effect of acute beta-adrenoceptor blockade with i.v. pindolol, acebutolol and atenolol has been studied at rest and during ergometric exercise, during routine intracardiac His bundle investigations. 2 At rest the functional parameters of the sinus node were impaired most markedly by atenolol. A-V nodal conduction was more depressed with acebutolol and atenolol than with pindolol. The His-Purkinje system conduction remained unaffected by all three beta-adrenoceptor blocking agents. 3 During ergometric exercise the depressant action of beta-adrenoceptor blockade on sinus nodal function with lower heart rates and on A-V nodal conduction with slower conduction velocities was equieffective with pindolol, acebutolol and atenolol. His-Purkinje system conduction again remained unchanged with one exception that after administration of pindolol, conduction rate during exercise was faster than before beta-adrenoceptor blockade. 4 It may be concluded that, in patients with low heart rates, an antagonist such as pindolol with relatively pronounced intrinsic sympathomimetic activity can be considered to be the drug of choice. In contrast, patients with higher heart rates at rest should be treated with a cardioselective betablocker without ISA. Patients with overt Sick Sinus Syndrome should not be given beta-adrenoceptor blockers at all. 5 Physical activity may change (improve or impair) the antiarrhythmic potency of beta-adrenoceptor blockers used in the treatment of supraventricular tachycardias or tachyarrhythmias.
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PMID:Electrophysiological effects of cardioselective and non-cardioselective beta-adrenoceptor blockers with and without ISA at rest and during exercise. 612 78

Oxprenolol is a nonselective beta-adrenergic blocking agent that also possesses intrinsic sympathomimetic activity (ISA) and membrane stabilizing effects. Oxprenolol undergoes first pass metabolism with only 30% of an oral dose reaching the systemic circulation. The drug is approximately 80% protein bound and is eliminated primarily by glucuronidation in the liver. Less than 4% of oxprenolol is excreted unchanged in the urine. Oxprenolol may reduce the heart rate and prolong the effective and functional atrioventricular nodal refractory period. Oxprenolol has less negative inotropic and chronotropic effects than propranolol. Plasma renin activity is reduced; however, changes in plasma aldosterone level are not significant. Long term metabolic effects require further study. Oxprenolol appears to be comparable to other beta blockers in the treatment of hypertension and angina pectoris with no additional adverse reactions. If its partial agonist effect proves useful, it may have an advantage over other agents in treating patients with borderline cardiac reserve. Because of limited data, the use of oxprenolol for the treatment of arrhythmias, migraine, thyrotoxicosis, anxiety, and glaucoma cannot be recommended at this time.
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PMID:Oxprenolol hydrochloride: pharmacology, pharmacokinetics, adverse effects and clinical efficacy. 634 36

Rats anaesthetized with pentobarbital and ventilated artificially were infused with 0.15 mg/kg/min. verapamil; without antidotal treatment, they died after 51.1+/-7.1 min. The survival time more than trebled upon an additional infusion with calcium chloride, epinephrine, isoprenaline, orciprenaline or prenalterol and nearly doubled upon administration of a plasma expander. It was not increased, however, by treatment with angiotensin or atropine. The infusion of verapamil declined the arterial blood pressure by 75%, and heart rate, cardiac output and peripheral resistance by about 50%; in the ECG, sinus bradycardia followed by AV-dissociation with nodal rhythm occurred. All antidotes that raised the lethal dose of verapamil increased the cardiac output. Calcium and the sympathomimetics with alpha-adrenergic activity also counteracted the verapamil-induced hypotension. Calcium did not influence the ECG alterations produced by verapamil, while the sympathomimetics restored the sinus rhythm or accelerated the nodal pacemaker. Calcium, epinephrine and isoprenaline also antagonized the strong decrease of left-ventricular dp/dt max. induced by verapamil. In conclusion, calcium as well as sympathomimetic amines are potent antidotes against the cardiovascular toxicity of verapamil, the latter being superior to calcium in their ability to improve pacemaker activity and AV-conduction.
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PMID:Antidotal treatment of the acute cardiovascular toxicity of verapamil. 650 11

We have investigated the effects of catecholamines (dopamine, norepinephrine, epinephrine and isoproterenol) and tyramine on sinoatrial conduction time (SACT), sinus cycle length (SCL) and developed tension (DT) in isolated atrial muscle, using an isolated and blood-perfused dog atrial preparation, perfused with heparinized blood from the carotid artery of the anesthetized donor dog. Each substance was continuously administered intraarterially into the cannulated sinus node artery. They had dose-dependent positive chronotropic and inotropic effects. Each produced not only a shortening but a prolongation of SACT. In experiments in which only a shortening occurred, the order of the potency for inducing the shortening of the SACT was isoproterenol greater than norepinephrine = epinephrine greater than dopamine greater than tyramine. The ratio of doses required to produce roughly a 15-25% shortening of the SACT was 1: 10: 10: 100: 300, respectively. The isoproterenol-induced shortening of the SACT was inhibited by treatment with propranolol. Tyramine-induced shortening was inhibited by imipramine. From these results, it is suggested that sympathomimetic amines induce a shortening of SACT through adrenergic beta-receptors and also readily induce a pacemaker shift in the SA nodal area.
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PMID:Direct effects of catecholamines and tyramine on sinoatrial conduction in isolated and blood-perfused dog atria. 674 20

To investigate how to reduce the positive chronotropic response to sympathetic nerve activation selectively without affecting other cardiac actions, we studied the effects of zatebradine, an inhibitor of the hyperpolarization-activated current (I(f)), verapamil and parasympathetic nerve stimulation on the positive chronotropic, dromotropic and inotropic responses to sympathetic nerve stimulation in the autonomically decentralized heart of the open-chest anesthetized dog. Parasympathetic input was activated by stimulation of the cervical vagus (CV) or parasympathetic nerves to the sinoatrial (SA) nodal region (SAP). Zatebradine (0.1-3 mumol/kg i.v.) decreased the heart rate but not other cardiac responses to sympathetic nerve stimulation, i.e., a wave component of the right atrial pressure (RAP), the first derivative of the RAP (dRAP/dt), atrioventricular (AV) conduction time (AVCT), right ventricular pressure (RVP) and its first derivative (dRVP/dt). Zatebradine (1 mumol/kg) inhibited basal heart rate by 28% but inhibited the chronotropic response to sympathetic stimulation by 85%. Verapamil (0.06-0.6 mumol/kg i.v.) attenuated the increases in heart rate, RVP and dRVP/dt elicited by sympathetic stimulation but potentiated shortening of the AVCT from the prolonged basal AVCT. The SAP stimulation attenuated the heart rate and dRAP/dt responses to sympathetic stimulation without affecting other cardiac responses, whereas CV stimulation decreased the positive chronotropic and atrial and ventricular inotropic responses. Cervical vagus stimulation did not change the positive dromotropic response. These results demonstrate that in contrast to CV nerve activation or verapamil, zatebradine and SAP stimulation cause bradycardia but preserve the myocardial contractile force and AVCT in response to sympathetic nerve activation or sympathomimetic drugs in the heart in situ.
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PMID:Selective inhibition by zatebradine and discrete parasympathetic stimulation of the positive chronotropic response to sympathetic stimulation in anesthetized dogs. 785 89

To verify, whether drugs used to treat hypertension, coronary disease, and heart insufficiency modify the hemodynamic effects of the combinations alfentanil-vecuronium and alfentanil-pancuronium, 36 patients taking these drugs (most often beta-adrenergic antagonists) were randomized to receive either vecuronium or pancuronium in connection with ophthalmic surgery. In comparison with healthy patients, the heart rate and arterial pressure changes during induction, intubation and surgery appeared to be smoothed. Heart rate and arterial pressure equaled between the study groups, indicating a block of the sympathomimetic actions of pancuronium. One third of the patients receiving vecuronium exhibited nodal rhythm and some of them showed slow heart rates during intense surgical stimulation. Pancuronium offered protection against bradyarrhythmias.
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PMID:Circulatory drugs modify the hemodynamic actions of alfentanil combined with vecuronium or pancuronium. 788 16


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