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The target-based drug discovery (TBDD) model relies on the following steps. Design a drug that binds to a molecular target, such as an enzyme or receptor. That binding affects the function of the target, leads to responses in the cell or tissue, and ultimately can affect the progression of a disease. These three stages – target binding, tissue response, and disease benefit – are relevant to drug discovery and development. Once a drug is approved and generally prescribed by healthcare providers, the terminology changes. The target bound by a drug and the drug’s effect on the target defines a drug’s mechanism of action. The response caused by target binding is called the mode of action. Finally, the disease being treated is the indication of the drug.
For example, consider the drug cimetidine. The mechanism of action of cimetidine is as a histamine H2 receptor blocker. So the target of cimetidine is the histamine H2 receptor, and cimetidine blocks the action of its target. The outcome of this mechanism is the mode of action, and cimetidine causes a reduction in stomach acid production. Through this mode of action, cimetidine treats gastroesophageal reflux disease (GERD), also known as acid reflux or heartburn. Acid reflux disease is cimetidine’s indication. Great. Next example.
Consider omeprazole. The mechanism of action of omeprazole is inhibition of the H+/K+ ATPase proton pump. These kinds of drugs are often called PPIs. The mode of action is reduction in stomach acid production. This is the same mode of action we saw with cimetidine. Both cimetidine and omeprazole have the same mode of action, but each drug achieves that mode of action through a different mechanism of action, by acting on a different target. Perhaps not surprisingly, both omeprazole and cimetidine, with the same mode of action, also have the same indication, treatment of acid reflux.
Another drug is dexamethasone. Dexamethasone’s target is the glucocorticoid receptor, and it activates the receptor. The glucocorticoid receptor plays roles in many response pathways in a cell, so dexamethasone shows multiple modes of action. Dexamethasone is an anti-inflammatory and reduces nausea (an antiemetic). The medical use of dexamethasone revolves mostly around its anti-inflammatory properties, and it is used to treat asthma, arthritis, and even immune response suppression. Dexamethazone has multiple indications.
Finally, consider eperisone. Eperisone’s target is not known, so it’s mechanism of action is also unknown. That may seem alarming, but it is OK. Drug regulators do not approve drug targets or mechanisms of action. They approve drugs on the basis of being safe and effective. Eperisone does have an effect, a mode of action. It relaxes skeletal and vascular smooth muscles to serve as an antispasmotic. Based on this mode of action, eperisone has found use treating conditions ranging from muscle weakness to forms of paralysis. Remember that not all drugs have a known target, and having a known target is not a prerequisite for approval of a new drug.
