On the simultaneous action of two competitive antagonists

1 A hypothesis is outlined predicting the conditions in which the addition of a second competitive antagonist will increase rather than reduce the response to an agonist.2 Experiments were performed with the guinea-pig ileum as the test tissue, hexyltrimethyl ammonium as the agonist, benzilyltropine methiodide as the ;slow' antagonist and pentyltriethyl ammonium as the ;fast' antagonist.3 The results are consistent with the hypothesis, if the affinity constant for hexyltrimethyl ammonium is between 2.7 and 3.7 x 10(4)M(-1), if the dissociation time constant for the slow antagonist is greater than 10 min and if that for the fast antagonist is less than 10 seconds.