Comparison of the beta2‐adrenoceptor selectivity of rimiterol, salbutamol and isoprenaline by the intravenous route in man.

Marlin, G. E.; Turner, Paul

doi:10.1111/j.1365-2125.1975.tb00470.x

Cited by 29 publications

(6 citation statements)

References 33 publications

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“…If the cat soleus muscle preparation is a predictive model for enhancement of physiological tremor in man, as has been suggested (Bowman & Nott, 1970) then all of the /3adrenoceptor agonists examined to date would be expected to enhance physiological tremor and cause bronchodilatation over the same dose-range when administered systematically. It is noteworthy that in the two studies reported in man in which this question has been examined in detail, the bronchodilator actions of salbutamol, terbutaline and rimiterol were accompanied by enhanced physiological tremor (Watson & Richens, 1974;Marlin & Turner, 1975). We therefore agree with the previous conclusions (Bowman & Nott, 1970;Bowman & Rodger, 1972) that it may prove impossible to separate the broncho-dilating and tremor-enhancing properties of /1adrenoceptor agonists except by giving the drugs by inhalation.…”

Section: Discussionsupporting

confidence: 89%

Selectivity of Β‐adrenoceptor Agonists and Antagonists on Bronchial, Skeletal, Vascular and Cardiac Muscle in the Anaesthetized Cat

Apperley

Daly

Levy

1976

British J Pharmacology

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I The potencies of fifteen /B-adrenoceptor agonists of widely differing chemical structures were compared with that of (-)-isoprenaline on bronchial muscle, soleus muscle, blood pressure and heart rate in the anaesthetized cat. The P-adrenoceptor antagonist potencies of propranolol and practolol were determined against (-)-isoprenaline in the same model. 2 (-)-Isoprenaline was the most potent agonist and its action was essentially unselective. Thus, on all four parameters the minimal effective dose was 0.003-0.01 .g/kg and maximal or near maximal responses were produced by 0.3-1 gg/kg. Trimetoquinol was also an essentially unselective agonist.3 For thirteen of the remaining fourteen agonists, potency was similar on bronchial muscle, soleus muscle and blood pressure but significantly lower on heart rate. 4 The remaining agonist AH 7616 (4-hydroxy-al-[[(1-methyl-3,3-diphenyl-propyl)aminolmethyll-m-xylene-al,a3-diol, acetate) -was also significantly less potent on heart rate than on the other parameters; in addition, it was clearly less potent on soleus muscle and blood pressure than on bronchial muscle when 5-hydroxytryptamine (5-HT) was used to induce bronchospasm. However, when acetylcholine was used instead of 5-HT the potency of AH 7616 on bronchial muscle, soleus muscle and blood pressure was very similar. AH 7616 may therefore possess a specific 5-HT antagonist action in addition to its,-adrenoceptor agonist action. 5The fifteen test agonists were longer acting than (-)-isoprenaline and this was particularly true of trimetoquinol and soterenol. 6 The /-adrenoceptor antagonist potency of propranolol was almost identical on bronchial muscle, soleus muscle and blood pressure and very slightly lower on the heart. Practolol was 10-12 times more potent on the heart than on bronchial muscle, soleus muscle and blood pressure. 7 These findings suggest that it may not be possible to separate the bronchodilating and tremorenhancing properties of /3-adrenoceptor agonists. The results with agonists and antagonists are in accord with Lands' dual /3-adrenoceptor sub-classification.

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Section: Discussionsupporting

confidence: 89%

Selectivity of Β‐adrenoceptor Agonists and Antagonists on Bronchial, Skeletal, Vascular and Cardiac Muscle in the Anaesthetized Cat

Apperley

Daly

Levy

1976

British J Pharmacology

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“…In view of this association of effects of sympathomimetic amines on the cat soleus and on slow motor units in man, the cat soleus preparation has been used to predict the tremorogenic activity of 0-adrenoceptor agonists in man. It is used in particular in the pre-clinical assessment of sympathomimetic bronchodilators, and its value in this respect has been substantiated by a correlation between the potencies of drugs in depressing the cat soleus (Bowman & Nott, 1970;Gwee et al, 1972;Houston & Rodger, 1974) and in causing tremor in man (Watson & Richens, 1974;Marlin & Turner, 1975). Because of its typical 0-adrenoceptor-mediated depressant action on the soleus, THP is thus likely to exert direct tremorogenic actions on muscle fibres of slow motor units in man.…”

Section: Discussionmentioning

confidence: 99%

Actions of Tetrahydropapaveroline on the Cardiovascular System and Skeletal Muscles of the Anaesthetized Cat and on Guinea‐pig Soleus Muscle in Vitro

Nott

Head

1978

Clin Exp Pharma Physio

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1. Tetrahydropapaveroline (THP) and isoprenaline have been compared for effects on heart rate, diastolic blood pressure and contractions of soleus and tibialis muscles in chloralose-anaesthetized cats and on in vitro guinea-pig soleus muscles. 2. All effects of THP were similar to those of isoprenaline. Maximal responses were the same and responses to both drugs were antagonized by propranolol. 3. THP produced an increase in heart rate, a fall in diastolic blood pressure and a decrease in the tension and degree of fusion of incomplete tetanic contractions of the soleus, being, respectively, 12.9, 14.7 and 19.6 times less potent than isoprenaline. The similarity in potency ratios suggests that THP is a non-selective beta-adrenoceptor agonist. 4. Effects on the guinea-pig soleus in vitro were similar to those in the cat soleus. 5. In the cat, THP enhanced the tension and duration of tibialis twitches, but the tibialis was about ten times less sensitive than the soleus to the effects of THP. 6. THP deepened neuromuscular blockade in partially curarized cat soleus and tibialis preparations. Doses required were ten times greater than for direct depressant effects on the soleus. 7. Agents which depress the tension and fusion of incomplete tetanic contractions of the cat soleus via beta-adrenoceptor stimulation cause tremor in man by peripheral effects on slow muscle fibres. THP is likely to exert such actions. This may explain why levodopa (a precursor of THP) sometimes precipitates a tremor crisis in Parkinsoniam patients, and why Parkinsonian tremor is relatively refractory to levodopa therapy. In such patients combination therapy with levodopa and a peripheral dopa decarboxylase inhibi;or (to reduce levels of THP) or a beta-adrenoceptor antagonist (to block the effects of THP on slow muscle fibres) could be advantageous.

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“…However in one patient (Case 5) salbutamol by constant IV infusion was effective in restoring normal ventilation without the tachycardia invariably present with isoprenaline. When equivalent doses of isoprenaline and salbutamol IV in man are compared, the former is 5 times more potent as a bronchodilator, and has a 10 times greater effect on heart rate (Marlin and Turner, 1975). Salbutamol by constant IV infusion has therefore fewer cardiac side effects and is now our first choice f-stimulant.…”

Section: Discussionmentioning

confidence: 99%

Severe ventilatory failure in asthma in children. Experience of 13 episodes over 6 years.

Simpson¹,

Mitchell²,

Inglis³

et al. 1978

Archives of Disease in Childhood

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(about 1 %) of 1225 admissions to hospital with asthma developed severe ventilatory failure (peak arterial Pco2 >8 kPa). Mean age was 4 v 1 years (2 * 3-7 * 9), and on average each patient had been admitted to hospital on 5 occasions during the preceding year. 11 gave a family history of asthma or a personal history of associated allergies. A viral upper respiratory tract infection was the commonest precipitant of wheeze, and in 7 patients the duration of wheeziness before admission to hospital was 12 hours or less. Six (0 5 %) patients were treated by mechanical ventilation and all survived. The changing patterns of management during the study period are reviewed.

show abstract

Comparison of the beta2‐adrenoceptor selectivity of rimiterol, salbutamol and isoprenaline by the intravenous route in man.

Cited by 29 publications

References 33 publications

Selectivity of Β‐adrenoceptor Agonists and Antagonists on Bronchial, Skeletal, Vascular and Cardiac Muscle in the Anaesthetized Cat

Selectivity of Β‐adrenoceptor Agonists and Antagonists on Bronchial, Skeletal, Vascular and Cardiac Muscle in the Anaesthetized Cat

Actions of Tetrahydropapaveroline on the Cardiovascular System and Skeletal Muscles of the Anaesthetized Cat and on Guinea‐pig Soleus Muscle in Vitro

Severe ventilatory failure in asthma in children. Experience of 13 episodes over 6 years.

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