In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor. Receptor sites have specific affinities for drugs based on the chemical structure of the drug, as well as the specific action that occurs there.
Drugs that do not bind to receptors produce their corresponding therapeutic effect by simply interacting with chemical or physical properties in the body. Common examples of drugs that work in this way are antacids and laxatives.
In contrast, a mode of action (MoA) describes functional or anatomical changes, at the cellular level, resulting from the exposure of a living organism to a substance.
Elucidating the mechanism of action of novel drugs and medications is important for several reasons:
Bioactive compounds induce phenotypic changes in target cells, changes that are observable by microscopy and that can give insight into the mechanism of action of the compound.
With antibacterial agents, the conversion of target cells to spheroplasts can be an indication that peptidoglycan synthesis is being inhibited, and filamentation of target cells can be an indication that PBP3, FtsZ, or DNA synthesis is being inhibited. Other antibacterial agent-induced changes include ovoid cell formation, pseudomulticellular forms, localized swelling, bulge formation, blebbing, and peptidoglycan thickening. In the case of anticancer agents, bleb formation can be an indication that the compound is disrupting the plasma membrane.
A current limitation of this approach is the time required to manually generate and interpret data, but advances in automated microscopy and image analysis software may help resolve this.
Direct biochemical methods include methods in which a protein or a small molecule, such as a drug candidate, is labeled and is traced throughout the body. This proves to be the most direct approach to find target protein that will bind to small targets of interest, such as a basic representation of a drug outline, in order to identify the pharmacophore of the drug. Due to the physical interactions between the labeled molecule and a protein, biochemical methods can be used to determine the toxicity, efficacy, and mechanism of action of the drug.
Typically, computation inference methods are primarily used to predict protein targets for small molecule drugs based on computer based pattern recognition. However, this method could also be used for finding new targets for existing or newly developed drugs. By identifying the pharmacophore of the drug molecule, the profiling method of pattern recognition can be carried out where a new target is identified. This provides an insight at a possible mechanism of action since it is known what certain functional components of the drug are responsible for when interacting with a certain area on a protein, thus leading to a therapeutic effect.
Omics based methods use omics technologies, such as chemoproteomics, reverse genetics and genomics, transcriptomics, and proteomics, to identify the potential targets of the compound of interest. Reverse genetics and genomics approaches, for instance, uses genetic perturbation (e.g. CRISPR-Cas9 or siRNA) in combination with the compound to identify genes whose knockdown or knockout abolishes the pharmacological effect of the compound. On the other hand, transcriptomics and proteomics profiles of the compound can be used to compare with profiles of compounds with known targets. Thanks to computation inference, it is then possible to make hypotheses about the mechanism of action of the compound, which can subsequently be tested.
There are many drugs in which the mechanism of action is known. One example is aspirin.
The mechanism of action of aspirin involves irreversible inhibition of the enzyme cyclooxygenase; therefore suppressing the production of prostaglandins and thromboxanes, thus reducing pain and inflammation. This mechanism of action is specific to aspirin and is not constant for all nonsteroidal anti-inflammatory drugs (NSAIDs). Rather, aspirin is the only NSAID that irreversibly inhibits COX-1.
Some drug mechanisms of action are still unknown. However, even though the mechanism of action of a certain drug is unknown, the drug still functions; it is just unknown or unclear how the drug interacts with receptors and produces its therapeutic effect.
In some literature articles, the terms "mechanism of action" and "mode of action" are used interchangeably, typically referring to the way in which the drug interacts and produces a medical effect. However, in actuality, a mode of action describes functional or anatomical changes, at the cellular level, resulting from the exposure of a living organism to a substance. This differs from a mechanism of action since it is a more specific term that focuses on the interaction between the drug itself and an enzyme or receptor and its particular form of interaction, whether through inhibition, activation, agonism, or antagonism. Furthermore, the term "mechanism of action" is the main term that is primarily used in pharmacology, whereas "mode of action" will more often appear in the field of microbiology or certain aspects of biology.