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Agonist and antagonist

An agonist is a chemical that binds to a receptor and activates the receptor to produce a
biological response. Whereas an agonist causes an action,
an antagonist blocks the action of the agonist.
Drug Receptor Interactions,
The two-state model of receptor activation
 The receptor is in two conformational states, ‘resting’ (R) and ‘active’ (R*), which
exist in equilibrium
 Normally, when no ligand is present, the equilibrium lies far to the left, and a few
receptors are found in the R* state
 For constitutively active receptors, an appreciable proportion of receptors adopt the
R* conformation in the absence of any ligand
 Agonists have higher affinity for R* than for R and thus shift the equilibrium from the
resting state (R) to the active (R*) state and hence, produce a response





Types of agonists
1. An endogenous agonist for a particular receptor is a compound naturally produced by the
body that binds to and activates that receptor. For example, the endogenous agonist
for serotonin receptors is serotonin, and the endogenous agonist for dopamine
receptors isdopamine.[1]
2. A superagonist is a compound that is capable of producing a greater maximal response
than the endogenous agonist for the target receptor, and thus has an efficacy of more than
100%. This does not necessarily mean that it is more potent than the endogenous agonist, but

7. 3. but have only partial efficacy at the receptor relative to a full agonist. an agonist or inverse agonist at that receptor Antagonist activity may be reversible or irreversible Types . E. anxiety. as they produce milder effects on the opioid receptor with lower dependence and abuse potential. muscle relaxation. A selective agonist is selective for a specific type of receptor.g. A co-agonist works with other co-agonists to produce the desired effect together.is rather a comparison of the maximum possible response that can be produced inside the cell following receptor binding. which mimics the actions of endorphins at μ-opioid receptors throughout the central nervous system. Another example is morphine. which mimics the action of adrenaline at β adrenoreceptors. One example of a drug that acts as a full agonist is isoproterenol. Full agonists bind (have affinity for) and activate a receptor. aripiprazole. glycine and D-serine co-agonists. Inverse agonists exert the opposite pharmacological effect of a receptor agonist. and controls convulsions.[2][3] 8. or norclozapine) also bind and activate a given receptor. An irreversible agonist is a type of agonist that binds permanently to a receptor through the formation of covalent bonds. buspirone is a selective agonist for serotonin 5-HT1A. The agonist action of benzodiazepines on the benzodiazepine receptor in the CNS produces sedation. NMDA receptor activation requires the binding of both glutamate. 5. An inverse agonist is an agent that binds to the same receptor binding-site as an agonist for that receptor and inhibits the constitutive activity of the receptor. buprenorphine. but blocks or reduces agonist-mediated responses”  Binding of antagonist to a receptor will inhibit the function of a partial agonist. not merely an absence of the agonist effect as seen with antagonist. Antagonists  Definition “An antagonist is a substance that does not provoke a biological response itself. b-carbolines (inverse agonists) which also bind to the same receptor cause stimulation. increased muscle tone and convulsions 6. Partial agonists (such as buspirone. A few of these have been described. Agents like buprenorphine are used to treat opiate dependence for this reason. producing full efficacy at that receptor. 4. even at maximal receptor occupancy.

Competitive irreversible antagonist  It binds to same site on receptor as agonist  The antagonist possesses reactive group which forms covalent bond with the receptor à the antagonist dissociates very slowly. or not at all  inhibition cannot be overcome by increasing agonist concentration (i.e.1-Competitive reversible antagonist  It binds to same site on receptor as agonist  inhibition can be overcome by increasing agonist concentration (i. It would either: bind to a distinctly separate binding site from the agonist àdecreased affinity of the receptor for the agonist..  Inhibition cannot be overcome by increasing agonist concentration (irreversible)  Example: the noncompetitive antagonist action of crystal violet (CrV) on nicotinic acetylcholine receptors is explained by an allosteric mechanism in which the binding of CrV to the extracellular mouth of the resting receptor leads to an inhibition of channel opening Physiological agonism describes the action of a substance which ultimately produces the same effects in the body as another substance—as if they were bothagonists at the same receptor—without actually binding to the same receptor.e. inhibition is reversible)  It primarily affects agonist potency  Example: Prazosin at a adrenergic receptors 2.. Physiological antagonism describes the behavior of a substance that produces effects counteracting those of another substance (a result similar to that produced by an antagonist blocking the action of an agonist at the same receptor) using a mechanism that does not involve binding to the same receptor. inhibition is irreversible)  Example: phenoxybenzamine at a adrenergic receptors 3.Non-competitive antagonist  It does not bind to the same receptor sites as the agonist. .

Physiological agonists  Epinephrine induces platelet aggregation. Pharmacokinetic antagonist Pharmacokinetic antagonist effectively reduces the concentration of the active drug at its site of action Example: phenobarbital accelerates the rate of metabolic degradation of warfarin . in contrast to histamine. epinephrine raises arterial pressure through vasoconstriction mediated by A1-adrenergic receptor activation. growth Physiological antagonists  There are several substances that have antihistaminergic action despite not being ligands for the histamine receptor. epinephrine and other such substances are physiological antagonists to histamine. Thus. they are physiological agonists to each other. despite not being true antihistamines because they do not bind to and block the histamine receptor. For instance. which lowers arterial pressure. Thus. and so does hepatocyte factor (HGF).