IN a previous paper [Gaddum and Hameed, 1954] we have summarized earlier work on antagonists for 5-hydroxytryptamine (HT) and described experiments with known drugs. The present paper gives the results of a study of the actions of a number of indole compounds in order to discover active antagonists. It was necessary to measure their potencies, and our attention was thus drawn to some of the difficulties which arise when antagonists are compared quantitatively with one another.Rough measurements may be made by finding the dose necessary to abolish the effect of the active drug (the "agonist") completely. Such measurements are unlikely to be very accurate since the result will depend on the dose used, and on the sensitivity of the record to small effects produced in the presence of the antagonist. Our own experience of this type of experiment confirms the impression that it is not very reliable. It is probably more satisfactory to use a method depending in some way on a measurement of the effect produced by the antagonist, and it is with such methods that this paper is mainly concerned.When the effect of a given dose of agonist is inhibited, it is generally found that larger doses are still effective, but can be blocked by larger doses of the antagonist. Such results are sometimes described by calling the antagonism competitive, but simple experiments of this type do not prove the theory that the two drugs are competing with one another for the same receptor in the tissue. Some other word is needed to describe the observation that an increase of dose of either drug overcomes the effect of the other. It is proposed to call antagonisms of this type surmountable, and to include in this group the antagonisms which have been called competitive, non-competitive and uncompetitive [Chen and Russell, 1950], as well as those which depend on the two drugs combining with one another to form an inactive complex [Gaddum, 1943]. Examples of unsurmountable antagonisms will be discussed later.

12 hr., then evaporated, and the residue extracted with ethyl acetate. Evaporation of the ethyl acetate gave a gum which was chromatographed in benzene on acid-washed alumina. Elution with light petroleuni-benzene (1 : 9) and evaporation of the eluate gave bright yellow

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