Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The aims of this study were to assess the relative beta 1/beta 2 selectivity of the antagonist and partial agonist activity (PAA) of celiprolol in man. 2. Eight normal males received single oral doses of celiprolol 200 mg (C200), 400 mg (C400) and 800 mg (C800); atenolol 50 mg (A50), 100 mg (A100) and 200 mg (A200); nadolol 40 mg (N40) and placebo (PL), administered in a single-blind, randomised crossover design. 3. At rest, in the presence of low levels of circulating adrenaline and noradrenergic tone, a low dose of celiprolol (C200) showed evidence of beta 1-PAA by significant increases in systolic blood pressure and resting heart rate. At higher doses (C400, C800), beta 2-PAA became evident by a significant increase in postural finger tremor, whereas C200 had no effect. 4. In the presence of a beta 1-adrenoceptor agonist, as assessed by reduction of exercise tachycardia, increasing doses of celiprolol produced significantly less beta 1-adrenoceptor blockade compared with atenolol. Furthermore, there was no increase in beta 1-adrenoceptor blockade beyond C400. 5. In the presence of a beta 2-adrenoceptor agonist, as assessed by blunting of terbutaline-induced chronotropic, hypokalaemic and finger tremor responses, celiprolol exhibited less beta 2-adrenoceptor blockade than comparable doses of atenolol used in clinical practice. 6. Exercise hyperkalaemia was blunted significantly by C400 and C800 in comparison with all doses of atenolol and nadolol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selectivity of antagonist and partial agonist activity of celiprolol in normal subjects. 133 81

1. The aims of this study were to investigate the partial agonist profile of carteolol and evaluate methodology for differentiating relative beta 1 and beta 2 partial agonist activity (PAA) in vivo. 2. Eight normal subjects received single oral doses of carteolol 10 mg, 30 mg and 60 mg; nadolol 40 mg; pindolol 30 mg and placebo, given in a single-blind, randomised crossover design. 3. beta 1-PAA was demonstrated with carteolol by dose-related increases in resting heart rate and systolic blood pressure, and a plateau in the dose-response curve for attenuation of exercise tachycardia. beta 2-PAA with carteolol was evidenced by a dose-related increase in resting finger tremor and progressive attenuation of exercise-induced hyperkalaemia. beta 2-adrenoceptor antagonism was shown by attenuation of terbutaline induced hypokalaemic, chronotropic and finger tremor responses. 4. Carteolol behaved as a non-selective beta-adrenoceptor antagonist with both beta 1 and beta 2-PAA components. In the standard clinical dose range of 10-30 mg, its in vivo PAA effects were relatively beta 1-selective. Thus at low doses, there appeared to be a dissociation between selectivity of antagonist and partial agonist activity. 5. Attenuation of exercise hyperkalaemia appears to be a novel and sensitive method for the evaluation of beta 2-PAA in vivo.
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PMID:Evaluation of in vivo partial beta 1/beta 2-agonist activity: a dose-ranging study with carteolol. 134 93

Six normal subjects were given once daily treatment for 15 days with placebo (PL), betaxolol 10 mg (B10), 40 mg (B40); atenolol 100 mg (A 100); and nadolol 40 mg (N40). Measurements of beta 1-adrenoceptorblockade (reduction of exercise heart rate) and of beta 2-adrenoceptor-blockade (attenuation of isoprenaline induced finger tremor) were made after the first, eighth and fifteenth doses of each drug. Plasma concentrations showed dose related increases between 10 mg and 40 mg doses of betaxolol, and there was significant drug accumulation at steady state compared with after single dosing. The reduction in exercise heart rate (EHR) with B10 was less in comparison with all other treatments. There were no significant differences in effects between single and chronic-dosing for any of the treatments (% reduction EHR compared with placebo, on days 1 and 15): B10 (18.2, 19.0), B40 (28.6, 26.5); A100 (22.7, 23.1); N40 (26.6, 23.8). Dose-ratios for attenuation of isoprenaline-induced finger tremor (IT100) were significantly greater with B40 compared with B10 or A100 (no dose-ratio for finger tremor could be calculated for N40). There were no differences between single and chronic-dosing (IT100 dose-ratios on days 1 and 15): B10 (3.0, 2.5), B40 (4.4, 5.3); A100 (3.0, 3.0). The attenuation of isoprenaline-induced chronotropic response (IH25) by N40 was significantly greater in comparison with all other treatments. IH25 dose-ratios (on days 1 and 15) were as follows: B10 (2.8, 3.6), B40 (5.1, 5.8); A100 (3.6, 3.6); N40 (19.0, 17.4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of chronic dosing on the beta 1 and beta 2-adrenoceptor antagonism of betaxolol and atenolol. 165 43

A dose-ranging study was performed to compare the beta 1-adrenoceptor selectivity of bisoprolol with that of atenolol and nadolol. Seven normal subjects (mean age 26 y) were given single oral doses of bisoprolol 5 mg (B5), 10 mg (B10), 20 mg (B20); atenolol 50 mg (A50), 100 mg (A100); nadolol 40 mg (N40); and placebo (PL), in a single blind randomised cross-over design. Beta 2-adrenoceptor responses were assessed by attenuation of finger tremor and cardiovascular responses to graded isoprenaline infusions. Dose-response curves were constructed, and doses of isoprenaline required to increase finger tremor by 100% (IT100), heart rate by 25 beats/min (IH25), SBP by 25 mmHg (IS25), cardiac output by 35% (IC35), and decrease DBP by 10 mmHg (ID10), after each treatment were calculated. These indices were compared with placebo response and expressed as dose-ratios. Exercise heart rate (EHR) was used to assess beta 1-adrenoceptor blockade. There were dose-related increases in plasma concentrations of bisoprolol and atenolol. Reduction of EHR was significantly less with B5 (16.8%) in comparison with all other treatments: B10 21.9%, B20 23.1%; A50 22.5%, A100 22.6%; N40 22.9%. There were small but significant reductions in isoprenaline-induced tachycardia with bisoprolol and atenolol, although mean dose-ratios were considerably less in comparison with N40 (IH25 dose-ratios): B5 2.55, B10 3.18, B20 3.93, A50 2.91, A100 4.89, N40 17.23. There were similar patterns for the other isoprenaline responses. These results show that conventional doses of bisoprolol (10 mg) and atenolol (50 mg) produced equal antagonism of beta 1 and beta 2-adrenoceptors, and therefore possess equal degrees of beta 1-adrenoceptor selectivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A dose-ranging study to evaluate the beta 1-adrenoceptor selectivity of bisoprolol. 167 75

In the normal heart the ratio of beta 1/beta 2-receptors in both atria and ventricles is about 75:25; in the failing heart the ratio is about 60:40. Stimulation of either beta 1- or beta 2-receptors results in a positive chronotropic and inotropic response. In the periphery, with the exception of lipolysis, renin release, control of intraocular pressure and intestinal relaxation, beta 2-related activity predominates. The nature of the beta 2-receptor is being unravelled and it has now been cloned. The beta-receptor antagonist is 'anchored' via disulfide bonding. Subsequent events involve the regulatory protein guanine nucleotide which couples the receptor to adenylate cyclase. beta-receptor density may by up- or down-regulated. beta-stimulation down-regulates (uncouples and internalizes or sequestrates) and beta-antagonism up-regulates beta-receptor numbers, but the functional implications of such changes are not always clear. A partial agonist occupies a receptor site and competitively inhibits the full agonist (e.g. noradrenaline). A partial agonist differs from a full agonist in that maximal response of a tissue is less. When background sympathetic activity is absent or very low a partial agonist will act as an agonist, e.g. increase heart rate, but when background tone is high the partial agonist will behave functionally as an antagonist, e.g. decrease heart rate. In animals partial agonist activity (PAA) can be assessed in many ways. In the catecholamine-depleted (reserpine or syrosingopine), vagotomized or pithed, intact animal beta-activity can be assessed via changes in heart rate, cardiac contractility and atrioventricular conduction. Isolated organs can also be used such as atria, papillary muscle, tracheal, mesenteric artery and uterine preparations. The choice of animal is important as marked species differences in response can occur. In man assessing PAA is difficult due to the presence of an intact sympathetic system: the problem can be overcome by autonomic blockade of constrictor and vagal reflexes with prazosin, clonidine and atropine but leaving the beta-receptor mediated responses unimpaired. beta 1- and beta 2-selective PAA can also be gauged via an increased sleeping heart rate (basal sympathetic tone) in the presence and absence of a beta 1- and beta 2-selective antagonist. beta 1-selective PAA can also cause an increase in resting systolic blood pressure, beta 2-selective PAA may be further assessed by a fall in DBP, increased blood flow, fall in peripheral resistance or increased finger tremor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Measurement and cardiovascular relevance of partial agonist activity (PAA) involving beta 1- and beta 2-adrenoceptors. 196 43

Selectivity for beta 1- and beta 2-receptors to xamoterol, prenalterol and salbutamol were tested using ICI 118 551, a specific beta 2-receptor antagonist. Measurements were made of heart rate at rest and exercise, blood pressure, forearm blood flow and finger tremor. The actions of xamoterol were similar to those previously demonstrated, and were unaffected by beta 2-blockade, indicating selectivity for the beta 1-receptor. Salbutamol was selective for the beta 2-receptor and prenalterol was active at both.
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PMID:Selectivity of xamoterol, prenalterol and salbutamol as assessed by their effects in the presence and absence of ICI 118 551. 197 92

1. Six normal subjects were given single oral doses of betaxolol 10 mg (B10), 20 mg (B20), 40 mg (B40), 80 mg (B80), propranolol 40 mg (P40), or placebo (PL) in a single-blind randomised cross-over design. 2. beta 1-adrenoceptor blockade was assessed by reductions in exercise heart rate. Betaxolol produced dose-related reductions in exercise heart rate (beats min-1) up to a ceiling at B40, after which B80 showed a lesser effect: (158 +/- 8 PL, 128 +/- 3 B10, 123 +/- 2 B20, 116 +/- 4 B40, 136 +/- 10 B80, 135 +/- 4 P40). All doses of betaxolol (except B80) produced greater reductions compared with P40: (B10 P less than 0.001, B20 P less than 0.005, B40 P less than 0.001). 3. beta 2-adrenoceptor blockade was assessed by attenuation of finger tremor and cardiovascular responses to graded infusions of i.v. isoprenaline. Dose-response curves were constructed and the doses required to increase heart rate by 25 beats min-1, finger tremor by 200%, calf blood flow by 0.5 ml dl-1 min-1, and decrease diastolic blood pressure by 10 mm Hg, after each treatment were calculated. These were then compared with placebo responses and expressed as dose-ratios. 4. Dose-ratios for finger tremor showed significant attenuation by all doses of betaxolol (compared with PL): B10 1.5 +/- 0.18 (P less than 0.05), B20 2.62 +/- 0.45 (P less than 0.005), B40 2.55 +/- 0.33 (P less than 0.001), B80 2.48 +/- 0.48 (P less than 0.01); and by P40 6.49 +/- 1.12 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A dose-ranging study to evaluate the beta-adrenoceptor selectivity of single doses of betaxolol. 197 96

This is the first report on the successful treatment of one patient with lithium induced tremor with hydrophilic atenolol, which is a relatively selective beta 1 adrenergic receptor blocker. Atenolol's advantages over lipophilic beta blockers in the treatment of lithium induced tremor are discussed.
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PMID:Treatment of lithium induced tremor with atenolol. 249 52

1. The purpose of the study was to assess and compare the effects of inhaled salbutamol on heart rate (HR), finger tremor (Tr) and specific airways conductance (sGaw) in the measurement of beta 2-adrenoceptor blockade in normal subjects. 2. Five healthy volunteers were given oral doses of atenolol 50 mg, 100 mg, 200 mg (A50, A100, A200), propranolol 40 mg (P40) or identical placebo (P1) in a single-blind crossover design. 3. Three hours after drug ingestion, dose-response curves were constructed using cumulative doses of inhaled salbutamol: 200 micrograms, 700 micrograms, 1700 micrograms, 3200 micrograms, 6200 micrograms. HR, Tr and sGaw were measured at each dose increment, made every 20 min. 4. Increasing doses of atenolol were associated with progressive reduction in salbutamol induced beta-adrenoceptor responses. The greatest attenuation occurred with propranolol. These effects on beta-adrenoceptor responses were similar for HR, Tr and sGaw. Geometric mean dose ratios (compared with placebo) for A50, A100, A200 and P40 were as follows HR: 1.98, 2.75, 4.29; Tr: 1.60, 3.78, 6.34, 80.50; sGaw: 1.08, 4.35, 12.30, 66.0 (no dose ratio was obtained for HR with P40). 5. These results showed that atenolol and propranolol attenuated the effects of salbutamol on HR to a similar degree as Tr and sGaw. Furthermore, the variability was least in the measurement of chronotropic responses, suggesting that this may be used to quantify beta 2-adrenoceptor antagonism. The beta 1-adrenoceptor selectivity of atenolol was a dose-dependent phenomenon, although the beta 2-adrenoceptor blockade of A200 was much less than with P40.
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PMID:Assessment of airways, tremor and chronotropic responses to inhaled salbutamol in the quantification of beta 2-adrenoceptor blockade. 257 Jun 1

We have studied the contribution of beta 1- and beta 2-adrenoceptors to the isoprenaline-induced changes in heart rate, blood pressure, forearm blood flow, peripheral vascular resistance, and finger tremor. This was achieved by a comparison of the effects of atenolol 50 mg, ICI 118551 25 mg, propranolol 80 mg, atenolol 50 mg combined with ICI 118551 25 mg, propranolol 80 mg combined with ICI 118551 25 mg, and placebo. Atenolol 50 mg and ICI 118551 25 mg caused similar attenuations in the isoprenaline-induced changes in heart rate and diastolic blood pressure, but the responses after the combination of atenolol and ICI 118551 were similar to those after propranolol 80 mg. There was no difference in the forearm blood flow responses to isoprenaline after atenolol 50 mg and ICI 118551, but atenolol 50 mg did not reduce peripheral vascular resistance compared with placebo. Both responses after treatment with atenolol combined with ICI 118551 were similar to those after propranolol 80 mg. Finger tremor responses to isoprenaline were antagonized by ICI 118551 alone and in combination with propranolol and atenolol but not by atenolol alone, suggesting that the response is beta 2-adrenoceptor-mediated. We conclude that the cardiovascular responses to isoprenaline are mediated by both beta 1- and beta 2-adrenoceptors, whereas the finger tremor response is mediated by beta 2-adrenoceptors.
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PMID:Characterization of the beta-adrenoreceptors which mediate the isoprenaline-induced changes in finger tremor and cardiovascular function in man. 285 55


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