Quantitative Studies of Antagonists for 5‐hydroxytryptamine

A number of synthetic indole compounds have been tested as antagonists for 5‐hydroxytryptamine (HT) in experiments on rat's uterus. 2. Antagonisms are classified as unspecific except when it has been possible to inhibit the response to HT without altering the response to acetylcholine. 3. The time course of the antagonisms has been followed by estimating the dose‐ratio: that is, the ratio of equiactive doses of HT before and after the administration of the antagonist. 4. The activity of different compounds has been compared by estimating the drug‐ratio, which is equal to the ratio of the dose of HT to the dose of antagonist, when the effect after 1 hour is 50 per cent of the original maximal effect. This gives results in general agreement with estimates of the pA 2 , and is more convenient when there are many substances to be tested. 5. The effects of the more active compounds, such as dibenamine, lysergic acid diethylamide and benzyloxygramine, developed slowly and became irreversible. Eventually the blockade could not be overcome even by enormous doses of HT, and it is then said to be unsurmountable. 6. The effects of less active specific antagonists (such as methylgramines) developed more rapidly, and were reversible and surmountable.