Agonist

An agonist is a ligand capable of binding to a receptor as a result of it's affinity to the given molecule, and causing a conformational change which stabilises the receptor in an activated conformation. The affinity of the ligand to the receptor is determined through molecular forces such as (in order of least to greatest strength) Vaan Der Vaals forces, ionic bonds, hydrogen bonds and covalent bonds. The presence of the receptor in an activated conformation allows for (mainly) cytoplasmic protein interaction and transmission of the signal into the cell, and an associated response e.g. increased gene expression. 

In terms of administration, agonists can be exogenous or endogenous molecules. The most common exogenous agonists that enter our body are actually unwanted, in contrast to desired administration of exogenous agonists e.g. medicines like morphine. Unwanted exogenous agonists can include chemicals produced in the work place, food additives, gaseous chemicals produced through pollution, second-hand smoke etc. Desired administration of exogenous agonists has many uses. Most common amongst these are pleasure (e.g. from ethanol), therapeutic effects (e.g. from aspirin) or religious experiences (e.g. entheogens). 

Endogenous agonists are molecules, typically synthesized or modified using metabolic pathways, present without prior administration. This does not mean however, that their quantity in the body is not alterable. For example, different levels of precursors to the final, endogenous agonists affect the level of the ligand. L-Dopa, a principal treatment for Parkinson's disease, is used in this way as it increases the levels of endogenous dopamine in the substantia nigra of affected patients. The level of gene expression is also important as it determines the quantity of enzymes capable of creating the final endogenous agonist. A greater amount of enzyme will increase the speed of synthesis of the final agonist, and thus increase it's effects. This provides insight into disease states, or predispositions to disease. For example, a lower expression of enzyme genes necessary to synthesize serotonin and noradrenaline can predispose people to lower mood states, and thus increase the likelihood of depression. 

Agonists are not only classified by their affinity to a given molecule (see first paragraph), but also by their efficacy. Efficacy is described as the ability of the agonists to stabilise the receptor into an activated state through a conformational change. A more full agonists will have the greatest efficacy possible and thus stabilise the receptor such that it remains active throughout the entirety of it's binding. A partial agonist with stabilise the receptor such that it remains active through a portion of it's bound time. As a result the full agonists will produce the greatest measurable response e.g. cause muscle contraction at it's limit. 

 

A partial agonist is a compound that binds to a receptor producing an incomplete response, therefore it is considered to be less potent.

The opposite of an agonist is an antagonist