Principles of Classification
The primary criterion used to classify drugs acting on receptors is intrinsic activity.
- If a substance binds to a receptor (possesses an affinity) and is capable of activating it, it is termed an agonist.
- If a substance binds but lacks intrinsic activity, it is an antagonist.
Agonists (mimetics) alter receptor conformation. This triggers a cascade of intracellular biochemical reactions, ultimately leading to a pharmacological effect.
Types of Agonists
Agonists are classified by their efficacy or stimulating strength at the receptor:
- Full agonists. Possess maximal intrinsic activity and are capable of producing the maximal possible effect for a given receptor system. For example, acetylcholine fully opens ion channels when binding to nicotinic receptors.
- Partial agonists. Their intrinsic activity is submaximal. Even if they occupy all available receptors, the effect will be weaker than that of a full agonist (e.g., buprenorphine).
- Inverse agonists. Act on spontaneously (constitutively) active receptors, shifting the equilibrium from the active state to the inactive state.
Mechanisms of Antagonism
Antagonists (or blockers) have affinity but lack intrinsic activity. Their function is to occupy the receptor and prevent endogenous ligands (hormones, neurotransmitters) or exogenous agonists from binding.
Antagonist effects are secondary: they eliminate the action of the natural stimulant, so the observed physiological effect is often the opposite of the agonist's action. For instance, acetylcholine causes bradycardia, whereas the antagonist atropine blocks this effect, resulting in tachycardia.
Antagonism is divided into two primary types:
- Competitive. Drugs compete for the same binding site. The outcome depends on relative concentration and affinity. The effect is reversible (surmountable)—adding a higher concentration of agonist will displace the antagonist. This principle is utilized in antidote therapy (e.g., physostigmine in atropine poisoning).
- Non-competitive. The antagonist binds to a separate (allosteric) site on the receptor or forms a tight covalent bond. The receptor undergoes a conformational change and cannot respond to the agonist. This type of antagonism is insurmountable: increasing the agonist dose does not restore the maximal effect.
Special Types of Interaction
Pharmacology also identifies substances with mixed mechanisms of action known as agonist-antagonists. They selectively interact with different receptor subtypes within the same system. For example, butorphanol blocks $\mu$-opioid receptors while stimulating $\kappa$-opioid receptors. This profile can reduce side effects compared to full agonists.
Partial agonists also exhibit unique behavior. By competing with full agonists for binding sites, they displace the latter. Because the intrinsic activity of the partial agonist is lower, the net effect is reduced. Thus, they can functionally act as antagonists in the presence of full agonists.