R. P. Stephenson, from the Department of Pharmacology at the University of Edinburgh, presents a modified receptor theory in this paper. He challenges the traditional view that drugs combine with tissue receptors to produce their effects, as proposed by Langley in 1878. Stephenson discusses Clark's attempts to quantify this concept using Langmuir's adsorption isotherms, but argues that the derived equations do not accurately describe the relationship between drug concentration and tissue response. Stephenson introduces three hypotheses to broaden the application of receptor theory: 1. A maximum effect can be achieved with only a small proportion of receptors occupied. 2. The response is not linearly proportional to the number of receptors occupied. 3. Different drugs have varying capacities to initiate a response, which is referred to as efficacy. He provides experimental evidence to support these hypotheses, particularly through the study of alkyltrimethylammonium salts (Alkyl-TMA) on guinea-pig ileum. Stephenson demonstrates that some Alkyl-TMA compounds exhibit intermediate effects, neither acting as true agonists nor antagonists. These partial agonists require a significant proportion of receptors to produce a response, which is consistent with the hypotheses. The paper also discusses the de-atropinization effect, where partial agonists oppose the action of atropine, further supporting the idea that these compounds occupy most receptors when producing a response. Stephenson concludes that the activity of acetylcholine-like drugs is due to both affinity for receptors and efficacy, and suggests that this dual property can explain most observed facts in drug action.R. P. Stephenson, from the Department of Pharmacology at the University of Edinburgh, presents a modified receptor theory in this paper. He challenges the traditional view that drugs combine with tissue receptors to produce their effects, as proposed by Langley in 1878. Stephenson discusses Clark's attempts to quantify this concept using Langmuir's adsorption isotherms, but argues that the derived equations do not accurately describe the relationship between drug concentration and tissue response. Stephenson introduces three hypotheses to broaden the application of receptor theory: 1. A maximum effect can be achieved with only a small proportion of receptors occupied. 2. The response is not linearly proportional to the number of receptors occupied. 3. Different drugs have varying capacities to initiate a response, which is referred to as efficacy. He provides experimental evidence to support these hypotheses, particularly through the study of alkyltrimethylammonium salts (Alkyl-TMA) on guinea-pig ileum. Stephenson demonstrates that some Alkyl-TMA compounds exhibit intermediate effects, neither acting as true agonists nor antagonists. These partial agonists require a significant proportion of receptors to produce a response, which is consistent with the hypotheses. The paper also discusses the de-atropinization effect, where partial agonists oppose the action of atropine, further supporting the idea that these compounds occupy most receptors when producing a response. Stephenson concludes that the activity of acetylcholine-like drugs is due to both affinity for receptors and efficacy, and suggests that this dual property can explain most observed facts in drug action.