Comparison of the effect of pindolol and propranolol on heart rate after acute and chronic administration.

Finch, MB; O'Connor, PC; Harron, D. W. G.; Shanks, R. G.

doi:10.1111/j.1365-2125.1983.tb01526.x

Cited by 4 publications

(1 citation statement)

References 17 publications

(21 reference statements)

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“…P-adrenoceptor antagonists with PAA reduce resting heart rate less than drugs devoid of PAA (Finch et al, 1983;Svendsen et al, 1981;Gugler et al, 1980). The lack of effect of Ro31-1118 on resting supine heart rate, which was reduced by atenolol, is suggestive of PAA, which animal studies have shown is a feature of Ro3l-1118 pharmacology (Blaber et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

Human pharmacokinetic and pharmacodynamic studies on Ro31‐1118, a new beta‐adrenoceptor antagonist.

O'Connor¹,

Arnold²,

Brown³

et al. 1985

Brit J Clinical Pharma

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1 The pharmacokinetic and pharmacodynamic effects of Ro31-1118 were examined in groups of healthy volunteers. 2 In three subjects given 10 mg of [14C]-Ro3l-1118 orally, peak levels of radioactivity (84 + 5 ng/ml) were 16 times those of the parent drug (-5 ng/ml). 3 Very little parent drug was recovered in the urine, although recovery of total radioactivity was nearly 80% in the urine by day 5. 4 In five subjects studied after both oral and intravenous administration of 20 mg Ro31-1118 the average bioavailability was 57% (range 41-73%).5 Following intravenous infusion the apparent volume of distribution for the five subjects averaged 590 1 (range 510-700 1). The elimination half-life averaged 18 h (range 17-26 h). 6 In eight subjects who received 40, 80, 160 and 320 mg of Ro31-1118 orally there was a linear relationship between dose and plasma concentration (r = 0.999) and between dose and AUC (r = 0.996).7 Ro31-1118 had no effect on resting heart rate whereas atenolol reduced resting heart rate up to 6 h after all doses. 8 The maximum reduction of an exercise tachycardia after Ro31-1118 (320 mg) was 23.13 + 0.7% and compared with atenolol (100 mg) was 28.2 + 1.25%. At 24 h the percentage reduction after Ro31-1118 was 21.5 ± 1.7%, while after atenolol the percentage inhibition had decreased to 11.1 + 1.6%. 9 In three subjects Ro31-1118 (160 mg) orally had no effect on resting heart rate, forearm blood flow and systolic blood pressure, while atenolol (50 mg) reduced all three parameters. Atenolol had little effect on resting finger tremor, but after Ro31-1118 there was an approximate three fold increase. 10 In these three subjects the isoprenaline heart rate dose-response curve was shifted to the right in a parallel manner by both drugs. The increase in forearm blood flow induced by isoprenaline was decreased more by atenolol than Ro3l-1118. 11 Most subjects complained of tremor and visual disturbances after 160 and 320 mg of Ro3l-1118. 12 We conclude that Ro31-1118 is a ,B-adrenoceptor antagonist with partial agonist activity and a long duration of action. Ro31-1118 is at least as cardioselective as atenolol.

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Section: Discussionmentioning

confidence: 99%

Human pharmacokinetic and pharmacodynamic studies on Ro31‐1118, a new beta‐adrenoceptor antagonist.

O'Connor¹,

Arnold²,

Brown³

et al. 1985

Brit J Clinical Pharma

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Effect on heart rate over 24 hours of pindolol administered for 14 days

Kantelip

Trolese

Cromarias

et al. 1984

Eur J Clin Pharmacol

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The effect on heart rate of pindolol 5, 15 and 30 mg/day, a beta-adrenoreceptor blocker possessing intrinsic sympathomimetic activity, administered to 8 healthy volunteers for 14 days was studied. Heart rate was continuously recorded over 24 h during placebo treatment before each sequence, every 2 days during treatment, and then on the 15th, 17th and 18th days. Pindolol in the three doses used had no significant effect on mean heart rate over 24 h. It tended to lower mean diurnal heart rate non-significantly between noon and 6 p.m. Pindolol raised nocturnal heart rate between midnight and 6 a.m. to a comparable extent at all the doses used. Sympathetic tone is at its lowest during that period, which makes it possible to detect the intrinsic sympathomimetic activity of pindolol. After cessation of treatment, a rebound effect was observed, cardioacceleration being most marked after 30 mg/day.

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Characterization of the beta-adrenoreceptors which mediate the isoprenaline-induced changes in finger tremor and cardiovascular function in man

Pringle¹,

Riddell²,

Shanks³

1988

Eur J Clin Pharmacol

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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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Comparison of the effect of pindolol and propranolol on heart rate after acute and chronic administration.

Cited by 4 publications

References 17 publications

Human pharmacokinetic and pharmacodynamic studies on Ro31‐1118, a new beta‐adrenoceptor antagonist.

Human pharmacokinetic and pharmacodynamic studies on Ro31‐1118, a new beta‐adrenoceptor antagonist.

Effect on heart rate over 24 hours of pindolol administered for 14 days

Characterization of the beta-adrenoreceptors which mediate the isoprenaline-induced changes in finger tremor and cardiovascular function in man

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