Agonists and antagonists

Agonists and antagonists Ligands Types of agonist-
Endogenous agonist
Super agonist
Full agonist
Partial agonist
Inverse agonist
Irreversible agonist
Properties of Antagonist :
Spare receptors
Addiction
Drug tolerance
Dependence
Tachyphylaxis
Idiosyncrasy
Allergy

1. Agonists and Antagonists Vijay S alvekar Dept. of Pharmacology GRY Institute of Pharmacy

2. Classification of ligands : Ligands are classified by effect upon binding to the receptor. Agonist LIGANDS Antagonist Ligands : The molecules that bind to receptors . It is any molecule which attaches selectively to particular receptors

3. Agonism and Antagonism Agonists facilitate receptor response Antagonists inhibit receptor response ( direct ant/agonists )

4. Agonist Derived from Latin word – contender. Aids in the enhancement of an action . Drugs that bind to physiological receptors and mimic the regulatory effects of the endogenous signaling compounds are termed agonists . Ligands that activate a receptor to produce a biological response are called agonists.

5. There are several types of agonists Receptors can be activated either by endogenous or exogenous , leads to change in the biological response. Types of agonist- Endogenous agonist Super agonist Full agonist Partial agonist Inverse agonist Irreversible agonist

6. Endogenous agonist : Naturally present in the body and bind to and activate the receptor Super agonist : Capable of binding to the receptor and producing a greater maximal response than the endogenous Agonist Full agonist – The ligands that increase the activity of the receptors & produce the maximal response . Ex .- Morphine ,mimics the action of endorphins at opioid receptors .

7. Partial agonist – These ligands partially increase the activity of the receptors but do not produce the maximal response like full agonist even when present in excess amount. Ex .- Buspirone , is an anxiolytic drugs , used to treat an anxiety disorder . Inverse agonist – The ligands which decrease the activity of an active receptors to their inactive state. Ex.- Flumazenil drugs acts as a inverse agonist for the GABA receptor & produce anxiogenic effect.

8. Irreversible agonist: binds and activates the receptor but the binding is permanent; so, this happens only once and the receptor is essentiallydestroyed

9. Antagonist Derived from Latin & Greek words – competitor or opponent . Opposes the action of agonist and block the reception . Ligands that block agonist mediated responses (rather than eliciting a biological response from binding itself) are called antagonists .

10. Properties of Antagonist : Site selectivity. Structural conformation – mimics with the natural ligand. Reduces the response. Effect may be temporary or permanent.

11. Competitive Types of antagonist- Ir r e v e r si b le Reversible No n - c omp e ti t i v e

12. The ant agonist competes with the agonist for the same receptor .

13. Non-competitive antagonists : The antagonist binds at a different site other than orthosteric site on the receptor. - The effect of the antagonist cannot be overcome by increasing the concentration of agonist . Ex.- Binding of cyclothiazide with mGLUR1 receptor.

14. Irreversible antagonists : May or may not competes with the agonist for orthosteric sites for binding to the receptor. Forms covalent bond to the site. . Ex .- Aspirin.

15. Spare receptors: Some tissues have more receptors than are necessary to produce a maximal response called spare receptor. Addiction : A brain disorder characterized by compulsive engagement in rewarding stimuli despite adverse consequences . Drug   tolerance  : A   pharmacological  concept describing subjects' reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug's effects ; however, this may accelerate  tolerance , further reducing the drug's effects .

16. Dependence: also known as drug  dependence , is an adaptive state that develops from repeated drug administration, and which results in withdrawal upon cessation of drug use. ... Compulsive and repetitive use may result in tolerance to the effect of the drug and withdrawal symptoms when use is reduced or stopped. Tachyphylaxis   : A medical term describing an acute, sudden decrease in response to a drug after its administration; i.e. a rapid and short-term onset of drug tolerance. It can occur after an initial dose or after a series of small doses . I diosyncrasy   : R efers to an idiosyncratic reaction, which is an adverse effect to an agent, such as a drug, which does not occur in most patients who've used the same agent. That shouldn't be too surprising .   A llergy:   the abnormal reaction of your immune system to a medication .