Drug Receptors

RECEPTORS

Concept first proposed at the beginning of the 20^th century.

Paul Ehrlich 1900----concept

J.N. Langley 1905– drugs may act on special sites or receptive substance.

RECEPTOR

Component of cell that interacts with a drug à initiates chain of biochemical reaction à

• The theory used in, Endocrinology, Immunology. & molecular biology

• Provides a mol. Basis for drug action

• Helps understand action & clinical use of drugs.

RECEPTOR– (Macromolecule with specific sites to which drugs ( ligands) bind) à change in macromoleculeà sets off a train of events à produces response of tissue or organ.

e.g. Contraction of smooth muscle, secretion of a gland. Release/inhibit neurotransmitters

• Receptors determine quantitative relationship

• between dose/conc. of drug & pharmacological effect.

• Receptor binding (affinity) determines conc. /required to form drug/receptor bonds.

• Total available receptors limit maximal effect

• RECEPTORSàselectivity of drug action.

• Binding to receptor depends onà mol. Size

Shape

Electrical charge

• Therefore change in chemical structure à will increase or decrease affinity for receptoràchanging effect

WHAT DO RECEPTORS DO?

1. no. of receptors limits maximal effect of drug

2. Affinity for binding determines the conc.of drug required drug-receptor units or complexes.

• Increased affinityàdecreased conc. of drug

• Decreased affinityàincreased conc. drug

3. Physical property of drug à mol. Weight, shape, electrical charge determines binding capacity with receptoràselectivity of drug action is produced.

4. Mediate action of antagonists

• Agonists change function of receptors by binding to it.

• Antagonists no change of function by binding. They block or prevent agonist action.

DEFINITIONS

AGONIST

A chemical substance (drug, hormone, or neuro transmitter) which combines with specific receptor. Activates it and produces a sequence of events.

Complete agonist activity is 1=max response.

Partial agonist activity/efficacy is less than 1.

ANTAGONIST

Interferes with action of agonist

ü Pure antagonistà no action of its own, but blocks agonist action.

E.g. Beta blockers à propanolol. Naloxone à opioid antagonist

ü Competitive antagonistàincreasing conc. of comp.antagonist progressively inhibits agonist response & vice versa.

ü Irreversible antagonist à affinity is increasedàreceptor occupancy increased

• Therefore agonist availability is decreased and maximum agonist response cannot be obiatained

Competitive & Irreversible Antagonists

Competitive & Irreversible Antagonists