describes the interaction between a drug and a receptor, which produces a biochemical and/or physiological response

A receptor is a small area of a macromolecule (mostly protein, but can be nucleic acids) on or in a cell. Upon stimulation, specific biochemical and /or physiological responses occur

Sequence of

REC

® CHANNEL

NT/H/DRUG->REC->CHANNEL OPENING -> FLOW OF ELECTROLYTES -> RESPONSE

Sequence of

REC

® SECOND MESSENGER SYSTEM

NT, H or DRUG->REC->G-PROTEIN (family, +,-) -> ENZYMES (adenylyl cyclase, guanylyl cyclase, phospholipase I, other )->SEC MESSENGERS

(cAMP,cGMP,IP3, DAG)-> ENZYME ACTIVATION, CHANNEL

OPENING -> RESPONSE

Sequence of REC

→ TRANSMEMBRANE ENZYME

Drug binding to different site which then influences this receptor

show affinity and intrinsic activity – cause a direct response

cause maximum biological response

cause less than maximum biological response, can be antagonists at high endogenous ligand activity

show only affinity, no direct response, block action

of endogenous compounds and reduce their actions

Reversible, competitive

Irreversible, noncompetitive

compete with endogenous compounds for receptors and they can be competed from the receptor by increasing concentrations of the native ligand or an agonist

bind covalently to receptors or allosterically and cannot be competed by increasing the concentrations of native ligands or agonists

Irreversible noncompetitive

Reversible noncompetitive

Van der Waals forces (weak), ionic bonds and/or hydrogen bonds; thus mostly reversible

Covalent bond is less frequent due to its irreversibilty

A + R

↔ A.R ↔ A.R* + response ↔ A + R

concentration of agonist or dose required to elicit half-maximal response

maximal response of agonist

            Drug-Receptor-complexes 

Drug concentration =    __________________   x Constant                    

                  Number of free receptors

response starts above a certain threshold number of receptors; usually graded (stepwise) and shows ceiling effect when all available receptors are stimulated 

Not all but a fraction of available receptors can be stimulated, remaining ones are not activated = spare receptors

True or False

Drugs with small margin of safety are safe

maximal effect of a drug

(number of receptors)

dose which produces a specific effect 

  (affinity of drug to receptor)