receptor ligands

The receptor is a macromolecule (mostly protein in nature and some are nucleic acids) having a specific ligand/drug binding site, located at the surface or inside the cells that serve to recognize the signals of ligands and initiate the response, but itself has no other function.

Ligands
The molecules having the affinity for the receptor and may alter the ongoing function. Ligands are generally categorized in to four types based on their affinity (ability to “bind to” the receptor) and efficacy (ability to cause a response via the receptor interaction; intrinsic activity):

Agonist
Antagonist
Partial Agonist
Inverse Agonist

1. Agonist

The biologically active compounds have the ability to bind with the receptor and activate the receptor to produce an effect similar to the endogenous physiological signaling molecules like neurotransmitters and hormones

Affinity = 1 (Max)
Efficacy = 1 (Max)

Examples: Salbutamol – Beta-2 receptor, Morphine – Opioid receptor, Barbiturates – GABA-A receptor

2. Antagonist (Receptor Antagonist)
The biologically active compounds which prevent the action of an agonist on a receptor by blocking the receptor; means they have the ability to bind with the receptor but do not activate/produce any effect

Affinity = 1 (Max)
Efficacy = 0 (Min)

Examples: Propranolol – blocks the Beta receptor, Prazosin – blocks alfa receptor, Atropine – blocks the muscarinic receptor

Antagonism
Antagonism is the term generally used in opposing the effects like

A) Functional/Physiological Antagonism: opposite action of two agonists that act at different receptors independent of each other but have opposite physiological effects.

e.g. acetylcholine activates the muscarinic receptor and decreases heart rate, while adrenaline activates the beta receptor and increase the heart rate

B) Competitive Antagonism (most common in clinical practice): An antagonist acts on the same site of the same receptor (only binds) of the agonist, preventing the binding and producing an effect by an agonist. Antagonist binding is reversible and can be overcome by a high dose of agonist.

C) Non-Competitive Antagonism: An antagonist acts on the allosteric site of the same receptor (only binds) of agonist or irreversible bind with the same site of the same receptor, prevent the binding and or producing an effect by an agonist. Irreversible binding can’t be overcome by a high dose of agonist.

3. Partial Agonist
The biologically active compounds activate a receptor to produce a submaximal effect.

Affinity = 1 (Max)
Efficacy = 0 to 1

Examples: Buprenorphine – partial agonist for opioid receptor

4. Inverse Agonist
The biologically active compounds bind and activate same receptor as an agonist but produce opposite pharmacological action.

Affinity = 1
Efficacy = 0 to -1

Examples: Beta carboline, DMCM – inverse agonist for GABA-A receptor, Chlorpheniramine – H1 receptor