The SELECTIVITY OF Β‐ADRENOCEPTOR ANTAGONISTS ON CARDIOVASCULAR AND BRONCHODILATOR RESPONSES TO ISOPRENALINE IN THE ANAESTHETIZED DOG

Daly, M.J.; Flook, Judith J.; Levy, Gerhard

doi:10.1111/j.1476-5381.1975.tb07347.x

Cited by 37 publications

(10 citation statements)

References 28 publications

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“…An ED50 of 0.038 mg ml-' was obtained for salbutamol which was not significantly different from that of salmeterol. Pretreatment of guinea-pigs with a P-adrenoceptor blocking dose of propranolol (1 mg kg' s.c.; Daly et al, 1975), prevented the inhibition of histamine-induced PPE by salmeterol (Figure 1). …”

Section: Lung Inflammationmentioning

confidence: 86%

Inhibition by salmeterol of increased vascular permeability and granulocyte accumulation in guinea‐pig lung and skin

Whelan

Johnson

1992

British J Pharmacology

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1. The long-acting P2-adrenoceptor agonist, salmeterol has been evaluated for its anti-inflammatory effects in the guinea-pig lung and skin. 2. Salmeterol, administered in bronchodilator doses to conscious guinea-pigs by both oral (0.01-1.0 mg kg-') and inhaled (nebulizer concentration, 0.001-1.0 mg ml-') routes, inhibited histamineinduced plasma protein extravasation (PPE) into the airway lumen. 3. Inhibition of PPE by salmeterol was long-lasting (>6 h) and was inhibited by prior administration of propranolol (1 mg kg-1, s.c.), indicating an effect mediated by P-adrenoceptors. 4. Inhaled salbutamol (nebulizer concentration, 0.00 1-1.0 mg ml-') also inhibited PPE in guinea-pig lung but, in contrast to salmeterol, this effect was short-lived with substantial loss of activity 2 h after administration. 5. Inhaled salmeterol (0.1 mg ml-') and salbutamol (1.0mg ml-') inhibited the accumulation of neutrophils in guinea-pig lung in response to lipopolysaccharide (100pgml-'). Salmeterol, but not salbutamol, inhibited the infiltration of eosinophils into the airway lumen in response to platelet activating factor (100 Lgml-'). These effects of salmeterol were blocked by prior administration of propranolol (5 mg kg-', s.c.), indicating that they were also P-adrenoceptor-mediated.6. Oral salmeterol (10mg kg-', p.o.), but not salbutamol (10 and 100mg kg-', p.o.), inhibited zymosan-induced granulocyte accumulation and PPE in guinea-pig skin. Lower doses of salmeterol (0.1 and 1 mg kg-') inhibited PPE, but not granulocyte accumulation. The effects of salmeterol were blocked by prior administration of propranolol (1mgkg-', s.c.). Both salmeterol and salbutamol inhibited histamine-induced PPE in guinea-pig skin.7. Intradermal salmeterol (10-'mol per site), but not salbutamol, was also effective in inhibiting zymosan-induced granulocyte accumulation and PPE in guinea-pig skin. 8. It is concluded that salmeterol, at bronchodilator doses in the guinea-pig, inhibits granulocyte accumulation and PPE, possibly by an action on the vasculature. As this profile of activity is not shared by the shorter-acting compound, salbutamol, it would seem that anti-inflammatory activity is associated with P-adrenoceptor agonism of long duration. The implications of these findings for the use of salmeterol in the treatment of bronchial asthma are discussed.

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Section: Lung Inflammationmentioning

confidence: 86%

Inhibition by salmeterol of increased vascular permeability and granulocyte accumulation in guinea‐pig lung and skin

Whelan

Johnson

1992

British J Pharmacology

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“…Since then many studies have confirmed that practolol has a greater affinity for cardiac than bronchial /5-receptors though the potency ratios have been variously reported as 100:1 and 2-3:1 in studies on anaesthetized dogs (Daly, Flook & Levy, 1975;Wasserman & Levy, 1974) whilst in human lymphocytes a ratio exceeding 5,000:1 has been reported (Conolly & Greenacre, 1977). The data most comparable to our own is a recent study of isoprenaline induced relaxation of histamine-induced contraction of human bronchial smooth muscle where a ratio of 15:1 was obtained (Davies, C., personal communication).…”

Section: Discussionmentioning

confidence: 99%

Quantitative assessment of bronchial beta‐adrenoceptor blockade in man.

Gribbin¹,

Baldwin²,

Tattersfield³

1979

Brit J Clinical Pharma

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I We describe a method for assessing bronchial ,B-adrenoceptor blockade quantitatively in man. Specific airway conductance is measured after increasing doses of inhaled salbutamol and the extent to which the dose-response curve is displaced to the right after f-adrenoceptor blocking drugs is used to assess bronchial ,B-adrenoceptor blockade. 2 Salbutamol dose-response curves were plotted for six normal subjects by measuring sGaw 15 min after increasing doses of inhaled salbutamol. Salbutamol produced a 30-70% increase in sGaw. 3 Salbutamol dose response curves were obtained 2 h after oral practolol (100 mg and 200 mg) and oral propranolol (40 mg and 80 mg) on separate days and were displaced to the right. 4 The mean dose ratios for practolol 100mg and 200mg were 1.2 and 2.1 and for propranolol 40 mg and 80mg they were 21 and 61 respectively.

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“…The a-and P-adrenoceptor blocking properties of labetalol and its stereoisomers were determined in anaesthetized dogs as described in detail by Daly, Flook & Levy (1975) and Kennedy & Levy (1975). In brief, beagle dogs of either sex, (7-11 kg) were 0007-1188/82/090105-10 $01.00 anaesthetized with thiopentone (25 mg/kgi.v) and barbitone sodium (250 mg/kg i.p.).…”

Section: Anaesthetized Dogsmentioning

confidence: 99%

The Α‐ AND Β‐ADRENOCEPTOR BLOCKING POTENCIES OF LABETALOL AND ITS INDIVIDUAL STEREOISOMERS IN ANAESTHETIZED DOGS AND IN ISOLATED TISSUES

Brittain

Drew

Levy

1982

British J Pharmacology

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103

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1 , The antagonist potencies of labetalol and each of its four stereoisomers have been compared at al-, Pl-and P2-adrenoceptors in anaesthetized dogs and in isolated tissues. 2 The RR stereoisomer is a potent, non-selective antagonist at P-adrenoceptors but has only weak al-adrenoceptor blocking activity.3 The SR stereoisomer was the most potent antagonist at ax-adrenoceptors, and it also had similar potency as an antagonist at j-adrenoceptors. 4 The a-and P-adrenoceptor blocking profile of the RS stereoisomer is intermediate between that of the RR and SR, but the SS stereoisomer is a relatively weak antagonist at both a-and P-adrenoceptors. 5 It is concluded that, although most of the ml-adrenoceptor blocking activity of labetalol is attributable to the SR stereoisomer and nearly all of its P-adrenoceptor blocking activity resides in the RR stereoisomer, each of the stereoisomers contributes to the overall pharmacological profile of labetalol.

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The SELECTIVITY OF Β‐ADRENOCEPTOR ANTAGONISTS ON CARDIOVASCULAR AND BRONCHODILATOR RESPONSES TO ISOPRENALINE IN THE ANAESTHETIZED DOG

Cited by 37 publications

References 28 publications

Inhibition by salmeterol of increased vascular permeability and granulocyte accumulation in guinea‐pig lung and skin

Inhibition by salmeterol of increased vascular permeability and granulocyte accumulation in guinea‐pig lung and skin

Quantitative assessment of bronchial beta‐adrenoceptor blockade in man.

The Α‐ AND Β‐ADRENOCEPTOR BLOCKING POTENCIES OF LABETALOL AND ITS INDIVIDUAL STEREOISOMERS IN ANAESTHETIZED DOGS AND IN ISOLATED TISSUES

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