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)

The central effects of phencyclidine (PCP) were investigated using electrophysiological, biochemical, and behavioral techniques. PCP produced depressions of neuronal firing of several brain regions when applied locally or parenterally. At the cerebellar locus coeruleus Purkinje neuron pathway PCP produced depressions of spontaneous firing. Use of lesion techniques and receptor antagonists revealed that at this synapse PCP acted as an agonist, i.e., an indirect sympathomimetic in that it caused release and or blocked reuptake of norepinephrine. PCP also produce alterations in behavioral measures such as stereotypy and rotarod performance. In addition PCP, like norepinephrine, produced increases in cyclic AMP levels in cerebellar slices. Inhibition of central neuron firing, and alterations in behavior were correlated with brain and blood levels of PCP. Many effects of PCP were antagonized by neuroleptics. It can be concluded that PCP has profound effects on several indices of central neuron function and such changes can be related to the psychosis and other effects of this drug.
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PMID:Candidate mechanisms underlying phencyclidine-induced psychosis: an electrophysiological behavioral, and biochemical study. 612 73

There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol (200mg daily), metoprolol (200mg daily); acebutolol (400mg daily), oxprenolol ( 160mg daily), nadolol ( 80mg daily) and timolol (20mg daily) produce a beneficial clinical response equal to that seen with propranolol ( 160mg daily). Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to control thyrotoxic hypercalcaemia. Minor side effects (nausea, headaches, tiredness, etc.) are quite common but overall beta-blockers are well tolerated by the thyrotoxic patient. The major use of these drugs is in symptomatic control while awaiting definitive diagnosis or treatment. As an adjunct to antithyroid drugs or radioactive iodine, beta-blockers will produce a satisfactory clinical response in the weeks to months before these forms of therapy produce a euthyroid state. beta-Blockers are more convenient than antithyroid drugs in the control of patients receiving therapeutic radioiodine, in that continuous therapy and assessment of biochemical response is possible.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Use of beta-adrenoceptor blocking drugs in hyperthyroidism. 614 1

Dose-dependent responses to L-isoprenaline of spontaneous activity and plateau height in Purkinje fibres can be mimicked closely by the PDE-inhibitor IBMX. Simultaneous applications of sympathomimetic amines and IBMX result in potentiated responses. The results support the hypothesis that cyclic-AMP is the common mediator of positive chronotropic and inotropic effects induced by beta-sympathomimetic amines.
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PMID:The effects of beta-sympathomimetic amines and phosphodiesterase inhibitors on electrophysiological parameters in Purkinje fibres. 615 87

Beta adrenoreceptor blocking drugs with high intrinsic sympathomimetic activity (pindolol and alprenolol) produced significant elevation of plasma cyclic AMP levels, when compared to propranolol. In hypertensive patients, despite these marked differences in plasma cyclic AMP levels, similar blood pressure control was achieved with these three beta blockers.
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PMID:The influence of beta blockers upon plasma cyclic AMP levels. 624 10

A study was performed to investigate changes in plasma cyclic adenosine monophosphate (cyclic AMP), peak expiratory flow and arterial blood gas tensions in response to running exercise and terbutaline sulphate aerosol in asthmatic patients regularly receiving sympathomimetic bronchodilator aerosols. Seven normal subjects were controls. Placebo aerosol was administered 20 min before the first exercise study and 1.0-1.25 mg terbutaline sulphate substituted 20 min after the first test and again 20 min before the second test. Blood gas tensions, expiratory flow and cyclic AMP were measured at rest, during and after exercise. Exercise induced a significant increase in cyclic AMP in both asthmatic and normal subjects. The change in plasma levels was not significantly different between groups. Cyclic AMP values were higher at rest and during exercise with terbutaline sulphate compared with placebo for both groups. Terbutaline sulphate blocked the marked fall in peak expiratory flow and arterial oxygen tension observed in the asthmatic subjects following the first test. Values for cyclic AMP following exercise were not significantly different between asthmatic and normal subjects. In contrast to other reports our asthmatics have a marked increase in cyclic AMP in response to exercise and to a beta-sympathomimetic aerosol.
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PMID:Plasma cyclic AMP levels in response to exercise and terbutaline sulphate aerosol in normal and asthmatic subjects. 625 59

Metabolic and cardiovascular effects of 4 mg oral salbutamol were studied in ten non-diabetic, ten chemical diabetic and five juvenile diabetic women in late pregnancy. None of the women had been treated with beta-sympathomimetic drugs earlier in their pregnancy. Heart rate and blood pressure were recorded and blood samples for measurement of plasma cyclic AMP, insulin, C-peptide, glucose, lactate, glycerol, non-esterified fatty acids (NEFA) and 3-hydroxybutyrate (3-HB) were collected every 30 minutes for 120 minutes after salbutamol. All women underwent the same procedure at random without salbutamol. There were significant cardiovascular effects of salbutamol in all the groups but no differences in these effects between the groups. Salbutamol caused significant increases of glycogenolysis and lipolysis in all the groups, significantly larger in the juvenile diabetic than the non-diabetic and chemical diabetic women. This observation could be explained by the inability of the juvenile diabetics to secrete insulin, shown by their non-measureable plasma C-peptide levels. The metabolic responses following salbutamol in the chemical diabetics were intermediate between the non-diabetic and juvenile diabetic groups. The results show that diabetes does not alter the sensitivity of beta-receptors involved in cardiovascular regulation, while the metabolic responses to oral salbutamol are enhanced, especially in juvenile diabetics. We suggest that during treatment with beta-sympathomimetic drugs, blood glucose should be monitored in all patients showing criteria of potential diabetes.
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PMID:Metabolic and circulatory effects of oral salbutamol in the third trimester of pregnancy in diabetic and non-diabetic women. 626 82

We studied the effect of posture on the sympathoadrenal response to intravenous theophylline in six normal subjects. On three separate occasions they received an intravenous infusion of either theophylline (6 mg/kg) while supine, theophylline (6 mg/kg) while standing or saline as placebo while standing. With the subjects standing theophylline caused tremor, a peak heart rate of 99 +/- 6 beats/min, and an elevation of plasma cyclic AMP from 9.3 +/- 0.7 to 15.1 +/- 1.7 nmol/1 (mean +/- s.e. mean). There was a small, but significant, elevation of plasma adrenaline, noradrenaline and glucose. The elevation in plasma catecholamines was insufficient to explain either the sympathomimetic effects of theophylline or the rise in plasma cyclic AMP. Theophylline had little or no effect with the subjects supine. The mean peak theophylline concentration following infusion was significantly higher with the subjects upright than when supine (18.3 c.f. 12.4 mg/l, P less than 0.025). However, adequate plasma levels of theophylline were obtained in all subjects when lying or supine. Analysis of individual data suggests that differences in plasma levels of theophylline are unlikely to account for the increased effects seen on standing. The mechanism of action of theophylline cannot be explained by increased secretion of catecholamines alone. Theophylline appears to amplify the increased sympathetic activity associated with standing and this is probably by phosphodiesterase inhibition.
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PMID:The effect of posture on the sympathoadrenal response to theophylline infusion. 631 28

The characteristics of the beta-adrenoceptors (3H-dihydroalprenolol binding) and the beta-adrenergic responsiveness (cyclic AMP response to isoproterenol) were studied in circulating lymphocytes from healthy volunteers before (D 0), on the 22nd day of treatment (D 22) and on the fifth day (D 30) following discontinuation of pindolol 15 mg/day or propranolol 160 mg/day. During pindolol therapy (D 22) the beta-adrenoceptor-affinity towards dihydroalprenolol was unchanged and the beta-adrenoceptor density decreased by 50%, an effect which persisted after drug administration ceased (D 30). The receptor "down-regulation" was accompanied by a parallel decrease in the maximal lymphocyte response to isoproterenol on D 22 and 30, by a shift to the right of the concentration-response curves to isoproterenol on D 22 and 30. In contrast, no significant modification in beta-adrenoceptor density or in the maximal response to isoproterenol was observed during (D 22) or after discontinuation (D 30) or propranolol therapy; the beta-adrenoceptor affinity for dihydroalprenolol and the sensitivity of the lymphocyte response to isoproterenol were markedly reduced on D 22 but not on D 30. It is concluded that the lymphocyte beta-adrenoceptor "down regulation" and the parallel beta-adrenergic desensitization induced by chronic pindolol therapy are both due to the intrinsic sympathomimetic activity of this drug.
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PMID:Comparison of changes in the characteristics of beta-adrenoceptors and responsiveness of human circulating lymphocytes during and after chronic administration of pindolol and propranolol. 632 5

Several possible mechanisms for 5-hydroxytryptamine (5-HT)-induced tachycardia in rat have been suggested: an activation of 5-HT1C or 5-HT2 receptors, an indirect sympathomimetic effect or a mechanism independent of 5-HT2 receptor stimulation. The aim of this study was to investigate the involvement of these mechanisms in the 5-HT-induced increase in rat atrial rate using biochemical methods. Indeed, the 5-HT1C and 5-HT2 receptors are linked to phosphoinositide hydrolysis and the noradrenaline (NA) released by 5-HT can stimulate the beta 1-adrenergic receptors linked to adenylate cyclase stimulation. The effect of varying concentrations of 5-HT on inositol phospholipid hydrolysis and adenylate cyclase activity of the rat isolated atria were measured. 5-HT (2 microM) did not modify total inositol phosphate (IP) production, while 5-HT 10 and 50 microM increased it 2-fold. The 5-HT2 antagonist ketanserin (1 microM) abolished IP accumulation induced by 5-HT microM), which indicates that this accumulation is 5-HT2 and not 5-HT1C receptor-mediated. Moreover, cyclic AMP (cAMP) formation was enhanced by 5-HT (5, 10, 20 and 50 microM). When atria were incubated 10 min with the beta-adrenergic receptor antagonist nadolol (1 microM), the increase in the cAMP level induced by 5-HT, whatever its concentration (10, 20 or 50 microM), was inhibited. Treating rats with reserpine (2.5 mg/kg, i.p., 48 and 24 hr before experimentation), which caused NA depletion in the heart, seemed to reduce the stimulating effect of 5-HT 10 and 50 microM on adenylate cyclase activity. Thus, the 5-HT-induced increase in cAMP is indirectly due to the activation of the beta-adrenergic receptors by the NA released by 5-HT. It is concluded that 5-HT stimulates both phosphoinositide turnover and adenylate cyclase activity in the rat isolated atria by activation of 5-HT2 receptors and by an indirect sympathomimetic effect.
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PMID:Biochemical characterization of the mechanisms involved in the 5-hydroxytryptamine-induced increase in rat atrial rate. 791 3

The intrinsic sympathomimetic activity (ISA) of a beta-adrenoceptor blocker can be mediated by beta(1)- or beta(2)-adrenoceptors. The aim of this study was to characterize the ISA of the beta-adrenoceptor blocker carteolol in healthy volunteers. Two approaches were employed. First, we assessed the effects of carteolol (20, 40 or 80 mg p.o.) on blood pressure, heart rate and heart-rate corrected duration of electromechanical systole (QS(2)c, a measure of cardiac contractility) in the volunteers. Carteolol dose-dependently increased systolic blood pressure, heart rate and contractility and decreased diastolic blood pressure. The beta(1)-adrenoceptor blocker bisoprolol did not attenuate these carteolol effects, but rather enhanced the effects on heart rate and systolic blood pressure. Second, we treated volunteers for 7 days with 1 x 20 mg/day carteolol and assessed lymphocyte beta(2)-adrenoceptor density (by (-)-[(125)I]-iodocyanopindolol binding) and functional responsiveness (by 10 muM isoprenaline-induced increase in lymphocyte cyclic AMP content). Carteolol significantly reduced lymphocyte beta(2)-adrenoceptor density and function. After withdrawal of carteolol lymphocyte beta(2)-adrenoceptor density and function recovered only very slowly and had not returned to control levels 11 days after carteolol withdrawal. In conclusion, the fact that, on the one hand, the cardiovascular effects of carteolol were not attenuated by the beta(1)-adrenoceptor blocker bisoprolol and, on the other, carteolol significantly decreased lymphocyte beta(2)-adrenoceptor density and function is in favour of the idea that the ISA of carteolol is mediated by beta(2)-adrenoceptors. Involvement of an additional receptor site (e.g. the propranolol-resistant state of the beta(1)-adrenoceptor), however, cannot be excluded.
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PMID:Beta 2-adrenoceptor-mediated intrinsic sympathomimetic activity of carteolol: an in vivo study. 1552 7


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