Comparison between the effects of inhaled isoprenaline and fenoterol on plasma cyclic AMP and heart rate in normal subjects.

Abstract

1 The time course of changes in plasma cyclic AMP, heart rate and bronchial tone after inhalation of fenoterol or isoprenaline from a dose-metered aerosol are reported in a group of normal subjects. 2 After isoprenaline, plasma cyclic AMP increased rapidly reaching a peak by 10 min and returned to basal levels within 60 min. A rapid, transient rise in heart rate occurred that was maximal by 5 min and returned to a basal level by 45 min. 3 After fenoterol, the changes in cyclic AMP and heart rate were of much longer duration. The rise in plasma cyclic AMP was slower in onset and of greater magnitude than for isoprenaline, reaching a peak by 20 min and remaining above basal level for more than 6 h. The maximum increase in heart rate after fenoterol was less than that observed with isoprenaline but an elevated rate persisted for 4 h after inhalation of fenoterol. 4 Fenoterol is known to have a longer duration of action as a bronchodilator in comparison with isoprenaline. The prolonged rise in plasma cyclic AMP in normal subjects given inhaled fenoterol may reflect this long duration of action. The concomitant rise in heart rate, however, suggests that the duration of plasma cyclic AMP response may in part be due to the systemic effect of the fraction of inhaled fenoterol known to be absorbed via the buccal and intestinal routes.

Pharmacological effects and pharmacokinetics of atipamezole, a novel alpha 2‐adrenoceptor antagonist‐a randomized, double‐blind cross‐over study in healthy male volunteers.

“…Cyclic AMP functions as the intracellular second messenger for ,-adrenoceptors, and the administration ofadrenoceptor agonists leads to increased concentrations of cAMP in plasma (Fairfax et al, 1984;Scheinin et al, 1987b). The observed increase in plasma cAMP levels after the highest dose of atipamezole was probably mainly caused by P-adrenoceptor stimulation from increased sympathetic activity and increased levels of circulating adrenaline, and cannot be used as evidence for direct participation of a2-adrenoceptors in the regulation of plasma cAMP levels.…”

Hypokalaemia and other non‐bronchial effects of inhaled fenoterol and salbutamol: a placebo‐controlled dose‐response study in healthy volunteers.

“…The tissue source of increased cAMP in plasma is somewhat uncertain, but the similar relationships to drug, dose and time observed for plasma K+ and cAMP in our study suggest a close relationship between the regulatory mechanisms; the common site of these drug actions may be skeletal muscle. Previously, 800 p,g inhaled fenoterol has increased cAMP in the plasma of healthy subjects by 200% (Fairfax et al, 1984). In another study, 600 ,ug inhaled fenoterol increased plasma cAMP by 56%, whereas 300 ,ug inhaled salbutamol elevated cAMP in plasma by only 18% in asthmatic patients obtaining similar improvement in airway resistance after both drugs (Endres et al, 1976).…”

“…Adrenaline, isoprenaline and selective P2-adrenoceptor agonists, but not noradrenaline, have increased cAMP levels in plasma; propranolol but not the pl-antagonist metoprolol has prevented this (Endres et al, 1976;Raij et al, 1976;Hjemdahl et al, 1983;Fairfax et al, 1984). The tissue source of increased cAMP in plasma is somewhat uncertain, but the similar relationships to drug, dose and time observed for plasma K+ and cAMP in our study suggest a close relationship between the regulatory mechanisms; the common site of these drug actions may be skeletal muscle.…”

Reproterol – A Monomolecular Combination of Orciprenaline and Theophylline: Novel Aspects of Its Mode of Action in Asthma

“…Inhalation of β 2 -agonists and co-administration of theophylline was shown to significantly increase cAMP production in vivo [19, 20, 21]. Further clinical studies are clearly needed to evaluate whether reproterol may favorably affect the airways compared to the effects of classic β 2 -adrenergics [22, 23].…”