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)

McN-2840-46, 2.5 mg/kg, i.v., protected against atrial tachyarrhythmias induced by three different methods in dogs and monkeys. The compound was inactive against ventricular arrhythmias produced by ouabain and by chloroform-epinephrine interaction at a four-fold higher dose. Significant reversal of ventricular arrhythmias produced by occlusion of the left anterior descending coronary artery in dogs was achieved by infusion of 8.8 +/- 2.4 mg/kg, i.v. of McN-2840-46. Myocardial electrogram studies confirm that the atrium is preferentially affected. McN-2840-46 does not possess beta 1- or beta 2-adrenergic blocking activity when evaluated on isolated rabbit atrial and guinea-pit tracheal chain preparations. McN-2840-46 is vagolytic but not anticholinergic. The vagolytic activity is attributed to its local anesthetic effect. Depression of myocardial function was observed in anesthetized dogs and in the heart-lung preparation. However, the isolated cat papillary muscle was stimulated by McN-2840-46 and doses considerably above the effective anti-arrhythmic dose did not significantly decrease cardiac output in the non-anesthetized dog. The results of these experiments suggest that McN-2840-46 is a potent "preferential" atrial anti-arrhythmic agent.
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PMID:Cardiovascular profile of 2-(3,4-diethyoxy-beta-methoxyphenethyl) imino-1-methylpyrrolidine fumarate (McN-2840-46), a preferential atrial anti-arrhythmic agent. 3 28

Electrophysiological changes produced by intravenous (0.1 mg/kg) metoprolol, a new selective beta 1-blocking agent devoid of intrinsic activity, were studied in 16 subjects with estimated normal impulse formation and conduction. The most important effects were sinus bradycardia, mild increase of sinoatrial conduction time, depression of intranodal conduction, and prolongation of AV node refractory periods. Sinus node recovery time and atrial refractory periods were unmodified. Infranodal conduction and the refractory periods of the His-Purkinje system, as well as of the bundle-branches, were unchanged. These effects are compared with those observed after intravenous propranolol, pindolol, and oxprenolol.
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PMID:Electrophysiological properties of intravenous metoprolol in man. 35 Feb 45

beta-Adrenoceptors were measured by saturation binding of [3H]CGP 12177 in nine brain regions and pineal from suicides, with a firm retrospective diagnosis of depression, and age and sex matched controls. Twenty one suicides had not recently received antidepressant drugs, 17 had been receiving drugs prior to death. In antidepressant drug-free suicides, the number of total beta-adrenoceptors was significant lower in temporal cortex (Brodmann area 38) and beta 1-adrenoceptors (Brodmann areas 21/22) was significant lower than matched controls. Suicides who died by violent means had significantly lower numbers of total beta- and beta 1-adrenoceptors in the frontal cortex and lower numbers of beta 1-adrenoceptors in temporal cortex (Brodmann areas 21/22) than matched controls. Suicides who died by non-violent means had lower numbers of total beta-adrenoceptors in occipital cortex controls and lower numbers of total beta- and beta 1-adrenoceptors in temporal cortex (Brodmann area 38) than matched controls. In antidepressant drug-treated suicides, significantly lower number of beta-adrenoceptor binding sites were found in temporal cortex (Brodmann area 38) and thalamus compared to matched controls. The lower number of beta-adrenoceptors binding sites in the thalamus appeared to be related to drug treatment. There were no differences in beta-adrenoceptor binding in the pineal gland between antidepressant-free and antidepressant-treated suicides and controls, although there were apparent differences between suicides and controls related to the time of death and season of death.
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PMID:beta-adrenoceptors in brain and pineal from depressed suicide victims. 136 71

Previously we have reported that rodent mast cells synthesize the mRNA encoding the alpha and beta integrin chains (alpha 4, beta 1 and beta 7) of the lymphocyte Peyer's patch adhesion molecule (LPAM)-1 and LPAM-2 lymphocyte homing receptors, and that they possess an alpha 4-containing integrin complex on their cell surface. In this report, we have examined the expression of these integrin chain genes by mature connective tissue mast cells (CTMC) and by bone marrow-derived mast cells (BMMC) differentiated from bone marrow precursor cells in the presence of interleukin (IL)-3 and/or the c-kit ligand (also known as mast cell growth factor and stem cell growth factor). High levels of both the beta 7 and beta 1 transcripts were present in mature CTMC while those encoding the alpha 4 chain were absent. Similarly, when BMMC were grown in IL-3 for 28 days and analyzed for integrin chain transcripts, those specific for the alpha 4 chain were also diminished compared to beta 7 and beta 1 transcripts. To compare the expression of these integrin genes during mucosal mast cell and CTMC development, BMMC were derived in the presence of IL-3 alone, c-kit alone, or IL-3/c-kit together. These experiments indicated that c-kit inhibited the transcription of the beta 7 and Fc epsilon RI genes while enhancing alpha 4 transcript levels. The enhancement of alpha 4 levels, however, was abrogated with the addition of IL-3. Similarly, the c-kit-induced depression of beta 7 and Fc epsilon RI transcript levels was overcome by the addition of IL-3. These data suggest that the integrin complexes synthesized by the mast cells may differ depending upon their path of differentiation and that another alpha chain integrin may be synthesized to complex with the beta 7 and/or beta 1 chains.
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PMID:Modulation of integrin expression during mast cell differentiation. 138 93

From clinico-pharmacological view the present paper gives a survey of the important drug group of the beta-receptor blockers. While non-selective blockers effect a global depression of the sympathico-adrenergic activity of the organism, the beta 1-selective blockers are characterized by a dose-dependent preferred affinity to the cardiac and renal beta 1-receptors. Thus in low and moderate dosages undesired pulmonary, vascular and metabolic effects can be avoided. Main indications for beta-receptor blockers are the arterial hypertension, the coronary heart disease and the tachycardiac disturbances of the cardiac rhythm. Apart from the increase of the life-quality of the patient the prognosis improving effect in clinical long-term studies confirmed for several beta-receptor blockers should be used therapeutically.
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PMID:[Beta receptor blockers. Their role and therapeutic importance]. 167 28

The enantiomers of formoterol (R;R and S;S) and their diastereomers (R;S and S;R) were synthesized and purified using a new procedure which required the preparation of the (R;R)- and (S;S)-forms of N-(1-phenylethyl)-N-(1-(p-methoxyphenyl)-2-propyl)-amine as important intermediates. The enantiomeric purity obtained was greater than 99.3%, usually greater than 99.7%. The four stereoisomers were examined with respect to their ability to interact in vitro with beta-adrenoceptors in tissues isolated from guinea pig. The effects measured were (1) relaxation of the tracheal smooth muscle (mostly beta 2), (2) depression of subtetanic contractions of the soleus muscle (beta 2), and (3) increase in the force of the papillary muscle of the left ventricle of the heart (beta 1). All enantiomers caused a concentration-dependent and complete relaxation of the tracheal smooth muscle which was inhibited by propranolol. The order of potency was (R;R) much greater than (R;S) = (S;R) greater than (S;S). There was a 1,000-fold difference in potency between the most and the least potent isomer. The presence of the (S;S)-isomer did not affect the activity of the (R;R)-isomer on the tracheal smooth muscle. Also on the skeletal and cardiac muscles (R;R)-formoterol was more potent than its (R;S)-isomer. The selectivity for beta 2-adrenoceptors appeared to be slightly higher for the (R;R)-isomer than for the (R;S)-isomer. The potency of the (S;R)- and (S;S)-isomers on the papillary muscle was too low to be determined accurately.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Steric aspects of agonism and antagonism at beta-adrenoceptors: synthesis of and pharmacological experiments with the enantiomers of formoterol and their diastereomers. 168 1

Cocaine-induced changes in respiratory rate (f), tidal volume (VT), total pulmonary ventilation (VE), dynamic lung compliance (Cdyn) and total pulmonary resistance (RL) were measured in anesthetized, spontaneously breathing Sprague-Dawley rats using a whole-body plethysmograph and an esophageal manometer. Carotid arterial pressure and heart rate were simultaneously monitored. An intravenous (i.v.) dose of 10 mg/kg of cocaine was lethal in all rats tested with death resulting from respiratory failure occurring between 0.25 and 1.5 min after dosing. At an i.v. dosage of 5 mg/kg, cocaine was nonlethal, although a reduction in VE was evident during the first minute after dosing. This reduction in VE was due to a decrease in f and the lack of a compensatory increase in VT. A slight decrease in RL also became evident approximately five minutes after dosing. Pretreatment with the nonselective alpha-adrenergic antagonist phentolamine (10 mg/kg) prevented the cocaine-induced depression in VE by reducing the decrease in f and blocking the inhibition of a compensatory increase in VT. In contrast, pretreatment with the nonselective beta-adrenergic antagonist propranolol (1 mg/kg) potentiated the cocaine-induced decrease in VE by enhancing the depression of f. Pretreatment with propranolol also caused a cocaine-dependent decrease in Cdyn. At a dosage of 0.3 mg/kg, labetalol, a compound possessing both nonselective alpha- and beta 1-antagonist activity (1:7) appeared to cause only a minimal potentiation of the cocaine-induced depressions in VE and f. Pretreatment with propranolol or labetalol also resulted in the death of 20% of the rats administered 5 mg/kg of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of adrenergic antagonists on cocaine-induced changes in respiratory function. 168 53

The short-term effects of oral diltiazem on hemodynamics and distribution of cardiac output at rest and during semiupright bicycle exercise were evaluated in eight patients with stable effort angina on long-term beta 1-adrenergic blockade. Cardiac output and iliofemoral blood flow were measured using thermodilution. The patients were exercised to the same work load on a bicycle before and 2 h after oral diltiazem (60 mg in two patients and 120 mg in six). At maximal exercise, diltiazem reduced heart rate from 94 +/- 5 to 88 +/- 6 beats/min (p less than 0.01), mean arterial pressure from 139 +/- 5 to 127 +/- 4 mm Hg (p less than 0.01) and systemic vascular resistance from 9.7 +/- 0.7 to 8.4 +/- 0.4 x 10(2) dynes.s.cm-5 (p less than 0.05) compared with control. During exercise, cardiac output, iliofemoral blood flow, mean pulmonary wedge pressure and mean right atrial pressure were not altered, but stroke volume increased from 119 +/- 11 to 131 +/- 10 ml (p less than 0.05). Maximal ST segment depression during exercise was decreased and angina was less. Diltiazem does not alter the distribution of the cardiac output during exercise but improves ischemia.
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PMID:Effects of diltiazem and long-term beta 1-adrenergic blockade on hemodynamics and blood flow during exercise in patients with stable angina pectoris. 196 60

A new cardioselective beta 1-adrenergic receptor agonist xamoterol (Corwin) has been developed for the treatment of heart failure. To study the acute hemodynamic effects of xamoterol, 24 patients, 39-70 years old, with mild-to-moderate postinfarction left ventricular dysfunction entered a double-blind, between-patient comparison of a single 5-minute intravenous infusion of xamoterol (0.2 mg/kg) and placebo. The acute hemodynamic effects of xamoterol were measured at rest and during two multistaged symptom-limited supine bicycle exercise tests (Ex-T), a control Ex-T followed by an Ex-T with either xamoterol or placebo. Compared with placebo, xamoterol significantly increased left ventricular contractility (Vmax and positive [+] dP/dt) and enhanced relaxation (dP/dt- and time constant relaxation) at rest and at the 25% and 50% levels of maximum exercise. The heart rate, the frequency and time to onset of anginal symptoms, the magnitude of exercise-induced ST segment depression, the left ventricular end-diastolic and peak systolic pressures, the mean pulmonary artery pressures, the cardiac index, the left ventricular stroke-work index, and the epinephrine and norepinephrine plasma levels at rest and during exercise did not differ significantly between placebo xamoterol groups. Thus, xamoterol can be a useful addition for the treatment of left ventricular dysfunction because of long-term ischemic heart disease.
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PMID:Improvement of left ventricular contractility and relaxation with the beta 1-adrenergic receptor partial agonist xamoterol at rest and during exercise in patients with postinfarction left ventricular dysfunction. A placebo-controlled randomized trial. 196 62

1. The beta-adrenoceptor affinity and blocking potency of the two enantiomers and the racemate of metoprolol were investigated in vitro, by use of a receptor-binding technique, and in vivo in the anaesthetized cat. 2. The enantiomeric purity of the S- and R-form was: greater than 99.2% and greater than 99.9%, respectively. 3. The beta 1- and beta 2-adrenoceptor affinity (-log equilibrium dissociation constant) of the enantiomers was determined from competition binding experiments (radioligand: [125I]-(S)-pindolol) performed in membranes prepared from the guinea-pig left ventricular free wall (predominantly beta 1) and soleus muscle (beta 2). The beta 1-adrenoceptor affinity was (means +/- s.d.): 7.73 +/- 0.10 and 5.00 +/- 0.06 for the S- and R-form of metoprolol, respectively. The corresponding values for beta 2-adrenoceptors were 6.28 +/- 0.06 (S) and 4.52 +/- 0.09 (R). Thus, the difference in affinity for the two enantiomers was greater on beta 1- (about 500) than on beta 2-adrenoceptors (about 50). The beta 1-adrenoceptor selectivity of the S-form (about 30) was similar to that of the racemic metoprolol, while the R-form was almost non-selective (3 fold beta 1-selective). 4. In the anaesthetized cat, the (-log) intravenous doses (mumol kg-1) of S- and R-metoprolol causing a 50% reduction (ED50) in the heart rate response to sympathetic nerve stimulation were determined. The doses inducing a 25% depression (DD25) of the basal myocardial contractility were also estimated. For the two enantiomers, the beta 1-blocking potency (-log ED50) was 7.04 +/- 0.16 (S) and 4.65 +/- 0.16 (R). A significant cardiodepressive effect was observed at high doses (-log DD25): 4.18 + 0.20 (S) and 4.08 + 0.10 (R). 5. It is concluded that the binding of metoprolol to beta 1-adrenoceptors has a stricter steric requirement than that for the binding of this beta l-blocker to beta 2-adrenoceptors. Furthermore, the non-specific cardiodepressive effect of metoprolol was observed at equally high doses for the two enantiomers.
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PMID:The beta 1- and beta 2-adrenoceptor affinity and beta 1-blocking potency of S- and R-metoprolol. 197 May 3


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