STUDIES ON THE MODE OF ANTAGONISM BETWEEN ADRENERGIC β-MIMETICS AND β-BLOCKING AGENTS (IV) INFLUENCE OF FUNCTIONAL ANTAGONISM BY SPASMOGENS

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Abstract
A new theory is presented to describe the effect of functional antagonism on the competitive antagonism between adrenergic .beta.-mimetics and .beta.-blockers in guinea pig tracheal preparations. According to this theory the shape of the log (dose ratio-1) vs. -log [B] curve and the apparent pA2 [scale for the measurement of drug antagonism, effective concentration of agonist to antagonist] value in competitive antagonism should be affected by functional antagonism when the agonist is taken up by the saturable uptake process, and this was experimentally confirmed. The competitive antagonism between isoproterenol (ISO) and propranolol (Prop) was influenced by the functional antagonism between ISO and spasmogens (histamine and carbachol). The log (dose ratio-1) vs. -log [B] curve of ISO-Prop competitive antagonism was shifted variously depending on the concentration of a spasmogen used. Theoretical predictions and experimental results were in good parallel.

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