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FUNCTIONAL ANTAGONISM AS A MEANS OF DETERMINING DISSOCIATION CONSTANTS AND RELATIVE EFFICACIES OF SYMPATHOMIMETIC AMINES IN GUINEA‐PIG ISOLATED ATRIA
Author(s) -
BROADLEY K.J.,
NICHOLSON C.D.
Publication year - 1979
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1979.tb10844.x
Subject(s) - orciprenaline , fenoterol , isoprenaline , chronotropic , chemistry , salbutamol , agonist , terbutaline , partial agonist , medicine , endocrinology , pharmacology , heart rate , receptor , biochemistry , asthma , stimulation , blood pressure
1 The positive inotropic and chronotropic responses to sympathomimetic amines were examined in guinea‐pig isolated atria. 2 The order of potency measured from EC 50 values was isoprenaline > orciprenaline > salbutamol ≥ fenoterol > terbutaline. Terbutaline and salbutamol were partial agonists on rate and together with orciprenaline and fenoterol also on tension responses. 3 Functional antagonism by carbachol caused a rightwards shift of the dose‐response curve and depression of the maximum response. The rate maxima for orciprenaline, fenoterol and terbutaline were above that of isoprenaline. All the tension maxima were below isoprenaline. 4 Dissociation constants ( K A ) and relative efficacies (e r ) were determined by analogy with irreversible antagonism. 5 The relative orders of affinity ( K A ) were isoprenaline > orciprenaline > fenoterol > salbutamol > terbutaline. Affinities were identical on rate and tension. 6 The relative efficacies were all greater than isoprenaline for rate responses. On tension they were the same or less than isoprenaline. 7 The implications of these results are discussed, in particular the fact that a partial agonist has a greater efficacy than a full agonist.