Intrinsic Activity: Function, Tasks, Role & Diseases

When binding to a receptor, ligands and drugs have an effect on the target cell. Intrinsic activity is the strength of this effect. Antagonists have zero intrinsic activity and are intended only to prevent other ligands from binding to the receptor in question.

What is intrinsic activity?

When binding to a receptor, ligands and drugs have an effect on the target cell. Intrinsic activity is the strength of this effect. From a chemical perspective, ligands are ions or molecules that are attracted to central atoms or central ions and form a complex bond with them. From a medical point of view, ligands are substances for receptor occupation that exert a receptor-mediated effect after binding to the receptor. In this context, intrinsic activity corresponds to the potency that a ligand or pharmacon possesses after binding to a specific receptor. Sometimes intrinsic activity also indicates the strength of the cell function change that occurs when ligands bind to receptors. Intrinsic activity plays a key role in pharmacodynamics in particular. This is the study of the action of drugs, which constitutes a branch of pharmacology. For example, the efficiency of a drug can be assessed via intrinsic activity. A special case of intrinsic activity is intrinsic sympathomimetic activity, also known as partial agonistic activity. This term refers specifically to the stimulatory effect of β-receptor blockers such as pindolol on their associated receptors. Intrinsic activity should be distinguished from affinity, which describes the attraction of binding partners. Meanwhile, intrinsic activity is sometimes referred to as efficacy.

Function and task

Each ligand has a specific site of action. This site of action is, for example, a cell membrane receptor. It is from this site that the ligand first exerts its effect on the cell. Together with a receptor, the ligand always forms a complex, the so-called ligand-receptor complex. Without this complex formation, the ligand cannot exert its effect. Upon binding, the resulting complex mediates a cellular effect that alters cellular functions. The alteration of cellular structures through the mediation of the ligand-receptor complex is the central element of intrinsic activity. It is not directly the alteration per se, but a measure of the strength of the cellular changes. In short, intrinsic activity is a measure of the effect strength of a particular ligand binding to a receptor. Intrinsic activity can be calculated. It is calculated using the formula IA = Wmax divided by Emax. IA in this formula stands for intrinsic activity. Wmax corresponds to the maximum possible effect of the agonist in question, and Emax is the theoretically maximum conceivable effect of the binding. With this formula, the values for intrinsic activity are always between zero and one. Thus, an agent or ligand with an intrinsic activity of zero does not elicit any effect via binding to the receptor. In this case, the active ingredient is said to be a pure antagonist, which only occupies the receptor and thus prevents other ligands from binding to the receptor. In contrast, when the intrinsic activity of an active ingredient is one, binding to the receptor achieves maximum effect. Thus, the ligand or drug cannot be called a pure antagonist. Agents with intrinsic activity between the values of zero and one are sometimes referred to as partial agonists. The classical model assumes “monofunctional” ligands acting at the receptor. In fact, however, a ligand is capable of targeting different signaling pathways individually. Ligands can also use different signaling pathways in parallel and thus act simultaneously as antagonist and agonist. Since intrinsic activity of a compound can vary from tissue to tissue.

Diseases and disorders

Intrinsic activity is ultimately relevant to all drugs. Agonists and antagonists are to be distinguished in this context. Antagonists, as mentioned above, have zero intrinsic activity. Accordingly, they do not exert any effect themselves but inhibit the action of other ligands of the receptor.Such drugs include beta blockers, for example. The active ingredient in these drugs binds to the beta receptors. In this way, they block the receptors for the binding of other substances whose effect is to be suppressed. For example, beta-blockers can bind to β-adrenoceptors. With this binding, they block bindings of the stress hormone adrenaline as well as the neurotransmitter noradrenaline. In this way, the effect of the substances is inhibited. In this way, the substances lower the heart rate at rest, for example. At the same time as this dampening effect, they also dampen blood pressure. For this reason, beta-blockers are used to treat various diseases and are suitable, for example, as a conservative drug therapy for high blood pressure or coronary heart disease. Because of their well-documented and now widely proven efficacy, beta-blockers are among the most frequently prescribed drugs of all. Agonists for dopamine receptors are used, for example, as active ingredients in the treatment of Parkinson’s disease. Agonists of these receptors include, for example, the substances budipine, cabergoline, dihydroergocryptine, lisuride, paliperidone, pergolide, piribedil, pramipexole or ropinirole. They improve typical symptoms of Parkinson’s disease due to the unfolded effect in receptor binding, such as, in particular, rigidity of movement, movement disorders, daytime fatigue and tremor.