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. The effects of treatment with bromoacetylalprenololmenthane (BAAM), an irreversible beta-adrenoceptor antagonist, for 30 min on the contractile responses of the rat left atria and portal vein have been determined. 2. On the electrically driven rat left atria, BAAM at 10(-5) M followed by a 60-min wash-out caused parallel rightward shifts of the isoprenaline response curves with no reduction in the maximal response to isoprenaline. 3. Treatment of the atria with BAAM at 3 x 10(-5) M caused non-parallel rightward shifts of isoprenaline response curves with a reduction in the maximum response to isoprenaline. The KA (dissociation constant) for isoprenaline at beta 1-adrenoceptors was 7.3 x 10(-7) M. Calculation of receptor occupancy demonstrated that in order to produce a maximal response of the rat left atria, isoprenaline had to occupy 12% of the beta 1-adrenoceptors. 4. Treatment of the atria with higher concentrations of BAAM (greater than or equal to 6 x 10(-5) M) caused a non-specific action, the reduction of the response to electrical stimulation. 5. On the rat portal vein, BAAM at 3 x 10(-7)-3 x 10(-6) M followed by a 45-min wash-out had no effect on the spontaneous contractile activity, caused non-parallel rightward shifts of isoprenaline response curves with a depression of the isoprenaline maximum responses. Using data derived from experiments with 3 x 10(-7), 10(-6) and 3 x 10(-6) M BAAM, the KA for isoprenaline at beta 2-adrenoceptor was 6.4, 3.7 and 7.7 x 10(-7) M and the calculated receptor occupancy was that in order to produce a maximal response of the rat portal vein, isoprenaline had to occupy 14, 21 and 12%, respectively of the beta 2-adrenoceptors. 6. The present study with the rat left atria and portal vein has shown that it is possible to determine treatments with BAAM that produce no non-specific actions and consequently BAAM may be used as an experimental tool in KA and receptor occupancy determinations in these tissues.
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PMID:Effects of bromoacetylalprenololmenthane (BAAM), an irreversible beta-adrenoceptor antagonist, on the rat isolated left atria and portal vein. 198 68

The autonomic components of the baroreflex control of heart rate were evaluated in conscious mongrel dogs before and after 4-6 weeks of ventricular pacing (250 beats/min). Arterial baroreflex sensitivity (BRS) was determined by the slopes of linear regression of pulse interval versus the preceding systolic arterial pressure in response to bolus injections of either phenylephrine or nitroglycerin. BRS was significantly depressed in the heart failure state [nitroglycerin slope, 5.0 +/- 2.7 (mean +/- SD) versus 16.6 +/- 5.1 msec/mm Hg, p less than 0.005; phenylephrine slope, 15.0 +/- 14.8 versus 32.0 +/- 26.7 msec/mm Hg, p less than 0.005]. There was no depression in BRS in dogs that were used as time controls or were acutely paced for 30 minutes. After beta 1-adrenergic blockade with metoprolol, the resting heart rate in the heart failure state was depressed more than in the normal state (-17.0 +/- 5.0% versus -3.2 +/- 3.4%, p less than 0.001). Atropine significantly increased resting heart rate more in the normal state than in the heart failure state (115.8 +/- 36.7% versus 25.4 +/- 14.5%, p less than 0.005). Thus, dogs in the heart failure state appear to have high resting cardiac sympathetic tone and low resting vagal tone. For nitroglycerin administration, metoprolol depressed BRS by 47.6 +/- 26.3% in the normal state and by 63.6 +/- 58.5% in the heart failure state. Atropine decreased the BRS by 86.7 +/- 7.8% in the normal state and by 39.5 +/- 30.2% in the heart failure state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of baroreflex control of heart rate in conscious dogs with pacing-induced heart failure. 198 84

beta-Adrenoceptor binding sites were quantitated by saturation binding of [3H]CGP 12177 in 9 brain regions from 21 suicide victims, with a firm retrospective diagnosis of depression, who had not recently received antidepressant drugs, and 20 age- and sex-matched controls. In depressed suicides the number of total beta-adrenoceptors was significantly lower in temporal cortex (Brodmann area 38, by 19%) and beta 1-adrenoceptors (Brodmann area 21/22, by 17%) compared to controls. Suicides who died by violent means had significantly lower numbers of total beta- and beta 1-adrenoceptors in frontal cortex than matched controls (by 23 and 25%, respectively) and than non-violent suicides (by 20 and 22%, respectively) and lower numbers of beta 1-adrenoceptors in temporal cortex (Brodmann area 21/22) than matched controls (by 16%). Depressed suicides who died by non-violent means had lower numbers of total beta-adrenoceptors in occipital cortex than matched controls (by 24%) and than violent suicides (by 18%), and lower numbers of total beta- and beta 1-adrenoceptors in temporal cortex (Brodmann area 38) than matched controls (by 27 and 24%, respectively). Depression in suicide victims is associated with deficits in beta-adrenoceptor binding sites, largely restricted to cortical areas.
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PMID:Brain beta-adrenoceptor binding sites in antidepressant-free depressed suicide victims. 217 63

Corwin is a new, long-acting beta 1-adrenergic partial agonist for oral and intravenous (i.v.) use. The effects of corwin were compared with those of dobutamine in acute ischemic left ventricular failure in dogs. Failure was produced by embolization of the left main coronary artery with 50 micron plastic microspheres. This induced severe depression in left ventricular function, as evidenced by a marked increase in left ventricular end-diastolic pressure, reduction in left ventricular dP/dtmax, and cardiac output. After 45 min was allowed for stabilization, the 27 dogs were randomly assigned to three groups: control (n = 9), dobutamine-treated (5-10 micrograms/kg/min i.v., n = 9), and corwin-treated (0.025-0.10 mg/kg i.v., n = 9). The doses of dobutamine and corwin were adjusted to give an increase in left ventricular dP/dtmax of 50%. Both drugs similarly increased cardiac output (p less than 0.01), lowered left ventricular end-diastolic pressure (p less than 0.01) and total peripheral vascular resistance (p less than 0.01), but did not affect the heart rate. Only dobutamine increased the mean arterial pressure (p less than 0.01). Both drugs also increased the arterial concentrations and myocardial uptake of fatty acids (p less than 0.05) but caused only a small and nonsignificant increase in myocardial oxygen consumption. Our findings indicate that the hemodynamic and metabolic profiles of corwin and dobutamine are similar, and both drugs should be of special value in the treatment of congestive heart failure. Since corwin can be given orally and has a longer duration of action, it is potentially useful in the long-term treatment of heart failure.
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PMID:Comparative effects of dobutamine and corwin, a beta 1-adrenergic partial agonist, in experimental left ventricular failure. 241 Jul 22

This report summarizes the most important results of 11 studies regarding efficacy and safety of bisoprolol in patients with stable angina pectoris due to coronary heart disease. Assessments carried out 2-3 h after the administration of the beta 1-selective adrenoceptor blocking agent bisoprolol revealed that the dose of 10 mg produced maximum effects in terms of improvement of exercise capacity (W X min) and reduction of ST segment depression at peak exercise. Duration of action was maintained over 24 h after administration of 5 and 10 mg bisoprolol. Thus, the data indicate no relevant loss of effect 24 h after single or repeated administration of 5-20 mg/day. Open uncontrolled long-term studies over 1 year demonstrated that bisoprolol in the dose range of 5-20 mg once daily is safe and highly effective. The evaluation was based on the bisoprolol effects on bicycle exercise tests, weekly anginal attack rates, the incidence of untoward side effects, and clinical routine laboratory investigations.
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PMID:Summary of short- and long-term studies with bisoprolol in coronary heart disease (CHD). 243 90

Celiprolol, a long-acting, beta 1-selective adrenergic blocking drug, with peripheral beta 2-stimulatory and peripheral alpha 2-inhibitory action, has a unique pharmacologic profile. Its antianginal properties have been evaluated in comparison with those of propranolol and atenolol. Efficacy was assessed by improvement in time to exercise-limiting angina and to onset of ST-segment depression, as well as by symptomatic improvement. Celiprolol has been demonstrated to have antianginal and anti-ischemic effects comparable with both propranolol and atenolol, with a decreased incidence of bradycardia noted in the celiprolol-treated cohorts. No significant adverse effects or laboratory abnormalities were noted in these cohorts. Current indications for beta-blocker therapy are numerous. Cardioprotective effects and reduction in ischemic potential have been identified in a variety of clinical settings. Decreased morbidity and mortality in the postinfarct period have been well documented. Effects on supraventricular and ventricular arrhythmias, in the presence or absence of ischemia, are well known. Favorable hemodynamic effects in the peri- and postoperative period of coronary artery bypass surgery are described. More recently, beta-blocker therapy that is effective against angina has also been demonstrated effective in the reduction of silent ischemia. The different hemodynamic properties of the newer beta-blockers may provide additional therapeutic effects in many clinical situations.
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PMID:Clinical performance and therapeutic potential of celiprolol in angina pectoris. 248 91

Investigations in animals indicate that urapidil has a number of actions that may be relevant to its antihypertensive effect. It has an alpha 1-blocking action, a weak beta 1-blocking effect, an interaction with a serotonin receptor and a central depression of sympathetic tone. Urapidil is well absorbed orally with a bioavailability of about 70% and a time to peak concentration of about 4 hours after a sustained release capsule. It is metabolized in the liver at a half-life of 4.7 hours. Peripheral alpha 1-blocking activity has been demonstrated in humans. A shift to the right in the dose-response curve to phenylephrine has been found after urapidil, whereas responses to angiotensin are not affected. Evidence for beta 1-blocking activity is marginal. Urapidil does not inhibit the exercise increase in heart rate. Some investigators have suggested a possible inhibition of isoprenaline tachycardia; others have found no evidence. There is some evidence suggestive of a central action of urapidil in humans as lower single doses result in a decrease in blood pressure and an increase in heart rate. With higher doses the hypotensive effect continues but the tachycardia no longer occurs. However, urapidil has been reported to increase noradrenaline levels, although there has been a report with a high dose reducing vanillylmandelic acid excretion. Evidence for changes in renin is inconsistent. Hemodynamic studies have revealed findings that are compatible with peripheral alpha 1 blockade. After intravenous administration, peripheral resistance is reduced along with arterial pressure, and cardiac output is increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urapidil, a multiple-action alpha-blocking drug. 256 63

1. The force of the electrically driven rat right ventricle strip is increased by isoprenaline but not by procaterol, a beta 2-adrenoceptor agonist. The effects of some beta-adrenoreceptor antagonists on the responses of the strip to isoprenaline have been determined. 2. Metoprolol (a beta 1-adrenoreceptor-selective antagonist) at 3 x 10(-8)-3 x 10(-7) moll-1 and ICI 118,551 (a potent beta 2-adrenoreceptor-selective antagonist) at 10(-7)-10(-6) moll-1 had no effect on maximum responses to isoprenaline and caused parallel rightward shifts of the isoprenaline response curves. The pA2 values for metoprolol and ICI 118,551 were 7.86 and 7.40, respectively. Thus the isoprenaline responses of the rat right ventricle strip are due to stimulation of beta 1-adrenoreceptors. 3. Metoprolol at 10(-6) moll-1 acted as a dual antagonist of the responses of the ventricle strip to isoprenaline causing parallel rightward shifts of the concentration-response curves which was due to beta 1-adrenoreceptor antagonism and a depression of the maximum response to isoprenaline which was probably due to membrane stabilizing activity. 4. Low concentrations of (+/-)-pindolol (10(-8) moll-1), (+)-pindolol (10(-7) moll-1), (-)-pindolol (10(-8) moll-1) and mepindolol (10(-10) moll-1) had no effect on isoprenaline maximum responses and caused parallel rightward shifts of isoprenaline response curves. Both (+/-)- and (-)-pindolol at 10(-7) moll-1, mepindolol at 10(-9)-10(-7) moll-1 and bopindolol at 10(-9)-10(-7) moll-1 reduced the isoprenaline maximum responses and caused non-parallel rightward shifts of the isoprenaline response curves. 5. BAAM (an irreversible beta-adrenoreceptor antagonist) treatment (3 x 10(-6) moll-1) for 30 min followed by 60 min washout reduced the isoprenaline maximum responses and caused a non-parallel rightward shift of the isoprenaline response curve. The kA (dissociation constant) for isoprenaline was 1.10 x 10(-6) moll-1. Calculation of receptor occupancy demonstrated that in order to produce a maximal response of the rat right ventricle strip, isoprenaline had to occupy 73% of the beta 1-adrenoreceptors. 6. The use of the rat right ventricle strip, a tissue with a small beta 1-adrenoreceptor reserve for isoprenaline, allows a definitive characterization of reversible (e.g. metoprolol) and irreversible (e.g. BAAM) beta 1-adrenoreceptor antagonists. It is suggested that (+/-)- and (-)-pindolol, mepindolol and bopindolol may be slowly dissociating beta 1-adrenoreceptor antagonists.
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PMID:The effects of beta-adrenoreceptor antagonists on the force responses of the electrically driven rat right ventricle strip to isoprenaline. 257 75

Some side effects of the beta 1-adrenoceptor blocker atenolol may result from depression of cardiac output at rest. They may, therefore, be reduced by the use of drugs with beta 1-partial agonist activity, such as epanolol. We compared once-daily atenolol 100mg and epanolol 200mg in 20 patients reporting side effects while taking atenolol for chronic stable angina. A double-dummy, double-blind, crossover design was used to assess side effects by use of visual analogue scales and interviews, and antianginal efficacy by treadmill exercise tests and diary cards. In a comparison with atenolol, no significant differences in exercise time (686 +/- 11 seconds vs 685 +/- 10 seconds, maximum ST depression (1.02 +/- 0.09mm vs 1.07 +/- 0.08mm), time to 1mm ST depression (8.4 +/- 1.9 minutes vs 9.0 +/- 2.0 minutes), or days without angina (median 100% in both) were shown. All visual analogue scores were higher with epanolol (subjective energy 58.3 +/- 1.7 vs 54.3 +/- 1.5, well-being 61.8 +/- 1.8 vs 58.6 +/- 1.5 and warmth of extremities 68.4 +/- 3.6 vs 62.0 +/- 3.1). Although these differences did not attain statistical significance, 11 patients expressed a preference for epanolol and only 6 for atenolol. We conclude that, in this study, epanolol is as effective as atenolol as an antianginal agent for chronic stable angina. It improved the side effect profile in some but not all patients.
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PMID:Effect of partial agonist activity on the side effects of beta-blockade in patients with chronic stable angina. 257 79

Extended (72-hour) ambulatory electrocardiographic monitoring was used to enable time series analysis of heart rate and asymptomatic ST-segment depression in 9 patients with severe coronary artery disease. The effects of beta 1-adrenergic blockade with optimal dose metoprolol were then assessed. Data were analyzed using Fourier transformation, autocorrelation and cross-correlation to examine possible coupling between heart rate and ischemic electrocardiographic changes. A marked circadian pattern was observed for both heart rate and ambulatory myocardial ischemia, with a period of approximately 24 hours by both Fourier and autocorrelation methods. Cross-correlation revealed heart rate and ischemia to be tightly coupled with a lag of 0 hours during placebo. During beta 1 adrenergic blockade the marked circadian variation in heart rate was diminished, although some periodicity in the 24-hour region remained. Ambulatory ischemia was also markedly diminished during beta 1-adrenergic blockade; however, some residual ischemia remained that was characterized by a peak spectral activity shifted to a period of 5 to 7 hours. Heart rate and ischemia were not coupled during beta 1-adrenergic blockade, as evidenced by lack of significant cross-correlation. Thus, time series analysis suggests close coupling between the variation in heart rate and ambulatory ischemia in patients with severe coronary artery disease. Beta 1-adrenergic blockade can markedly alter the periodic characteristics of and coupling between heart rate and ischemia. Ischemia remaining during beta 1-adrenergic blockade may have different spectral characteristics than that predominating during placebo administration. These differences may be manifestations of the heterogenous pathophysiologic mechanisms responsible for ambulatory ischemia and may have therapeutic implications.
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PMID:Influence of beta-adrenergic blockade defined by time series analysis on circadian variation of heart rate and ambulatory myocardial ischemia. 280 49


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