The assessment of beta‐adrenoceptor blocking drugs in man.

Bronchial and cardiac beta‐adrenoceptor blockade have been compared in six normal subjects after three beta‐adrenoceptor antagonists. Single and double doses of atenolol (50 and 100 mg), acebutolol (100 and 200 mg) and labetalolol (150 and 300 mg) were studied on separate occasions. 2 Salbutamol airway dose‐response curves were obtained by measuring the airway response as the change in specific airway conductance (sGaw) after increasing doses of inhaled salbutamol. Bronchial beta‐adrenoceptor blockade was assessed after each drug as the dose of salbutamol needed to cause a 50% increase in sGaw (sGaw D50). 3 Cardiac beta‐adrenoceptor blockade was assessed after the same doses of each beta‐adrenoceptor antagonist, by measuring the percentage reduction in exercise heart rate from control, after exercise for 5 min at 70% of the subject's maximum work rate. 4 Atenolol 50 and 100 mg caused least bronchial beta‐adrenoceptor blockade and the greatest reduction in exercise heart rate. 5 Acebutolol 100 and 200 mg and labetalol 150 and 300 mg produced more bronchial beta‐adrenoceptor blockade than atenolol. 6 With this approach new beta‐adrenoceptor antagonists can be assessed without putting asthmatic patients at risk.

Section: Discussionmentioning

confidence: 68%

Bronchial and cardiac beta‐adrenoceptor blockade‐a comparison of atenolol, acebutolol and labetalol.

Gribbin¹,

Mackay²,

Baldwin³

et al. 1981

“…Blockade of cardiac Pl-adrenoceptors is often assessed by the inhibition of an exercise tachycardia (McDevitt, 1977). This study has demonstrated that ICI 141,292 is an effective Iadrenoceptor antagonist with a long duration of action in man.…”

Section: Discussionmentioning

confidence: 92%

Effects of ICI 141,292 on exercise tachycardia and isoprenaline‐induced beta‐adrenoceptor responses in man.

Pringle¹,

O'Connor²,

McNeill³

et al. 1986

1 The P-adrenoceptor blocking properties and cardioselectivity of ICI 141, 292 were investigated in healthy male subjects. 2 Seven subjects received in random order oral doses of ICI 141,29220,50,100,200 and 400 mg, atenolol 50 and 100 mg and placebo. ICI 14292 had no effect on supine heart rate which was reduced by atenolol 100 mg. ICI 141,292 50, 100 and 200 mg had no effect on standing heart rate which was reduced by 400 mg at 2 h. Both doses of atenolol caused greater reductions. 3 The maximum percent reduction of an exercise tachycardia after ICI 141,292 200 mg (23.9 ± 3.7%) and 400 mg (24.3 + 5.2%) were similar to atenolol 50 mg (27.3 + 4.7%) but less than atenodol 100 mg (30.8 + 2.9%) (P < 0.02). 4 Six subjects received in random order single oral doses of ICI 141,292 100, 200 and 400 mg, atenolol 50 mg, propranolol 40 mg and placebo. Following each dose each subject received graded infusions of isoprenaline sulphate until heart rate increased by 40 beats min-'. Dose-response curves were constructed for the changes in heart rate, finger tremor, blood pressure and forearm blood flow produced by each infusion. 5 At the 4 ,ug min-' dose of isoprenaline, ICI 141,292 200 mg caused more attenuation than atenolol 50 mg but less than propranolol 40 mg in the changes of heart rate, diastolic blood pressure and finger tremor (P < 0.02). ICI 141,292400 mg caused more attenuation of the changes of all parameters than atenolol 50 mg but less attenuation of the changes in diastolic blood pressure and finger tremor than propranolol 40 mg (P < 0.02). 6 These results indicate that ICI 141,292 is a cardioselective ,-adrenoceptor antagonist with partial agonist activity.

“…Thus ICI 118,551 appears to have a direct effect on the isoprenaline-induced changes in heart rate. In view of the other results from this study, it would appear that the 02-adrenoceptors in the heart are functionally active (Ablad etal., 1974;Brodde et al, 1983 with cardioselective drugs (Dunlop & Shanks, 1968;McDevitt, 1977), but though the presence of such a reflex has been confirmed, it does not account for all of the observed differences between these two, types of drugs .…”

Section: Studymentioning

confidence: 99%

Effects of the beta 2‐adrenoceptor antagonist ICI 118,551 on exercise tachycardia and isoprenaline‐induced beta‐adrenoceptor responses in man.

Arnold¹,

O'Connor²,

Riddell³

et al. 1985

Self Cite

ICI 118,551, 5 to 80 mg orally, did not significantly alter resting heart rate or blood pressure. In doses less than 40 mg the reduction in exercise tachycardia was under 10 beats/min. ICI 118,551, 10 to 40 mg, did not appear to reduce the maximum rise in systolic pressure with isoprenaline but did attenuate the changes in diastolic pressure, forearm blood flow and finger tremor. It also attenuated the isoprenaline‐induced changes in serum glucose, insulin and potassium. On these observed changes, the effect of ICI 118,551 20 mg was similar to that of 40 mg and of propranolol 10 mg, but greater than that of atenolol 25 mg. An isoprenaline tachycardia was attenuated by all doses of ICI 118,551 studied. After atropine (0.04 mg/kg) ICI 118,551 20 mg still significantly reduced the effects of isoprenaline suggesting that functional beta 2‐adrenoceptors may be present in the human heart. In doses less than 40 mg, ICI 118,551 appears to be a selective and competitive antagonist of beta 2‐adrenoceptors in man.