Drug-Receptor Binding and Receptor Types Pharmacology I BMS 242 Lecture 5 Pharmacodynamics Drug-Receptor Binding and Receptor Types Dr. Aya M. Serry 2016

Effect of the Drug on the Body Pharmacodynamics Pharmacodynamics Effect of the Drug on the Body

Pharmacodynamics Pharmacodynamics describes the actions of a drug on the body and the influence of drug concentrations on the magnitude of the response Most drugs exert their effects, both beneficial and harmful, by interacting with receptors (that is, specialized target macromolecules) present on the cell surface or within the cell. A Receptor is: Pharmacology defines a receptor as any biologic molecule to which a drug binds and produces a measurable response The drug–receptor complex initiates alterations in biochemical and/or molecular activity of a cell by a process called signal transduction

Signal transduction Drugs act as signals, and their receptors act as signal detectors. Many receptors signal their recognition of a bound drug by initiating a series of reactions that ultimately result in a specific intracellular response

Signal transduction The drug–receptor complex Drug + Receptor Drug–receptor complex → Biologic effect Cells have different types of receptors, each of which is specific for a particular ligand and produces a unique response. The heart, for example, contains membrane receptors that bind and respond to epinephrine or norepinephrine as well as muscarinic receptors specific for acetylcholine These receptors dynamically interact to control the heart’s vital functions. Most receptors are named to indicate the type of drug/chemical that interacts best with it. For example, the receptor for histamine is called a histamine receptors.

Receptor Types Receptor types can be divided into four families ( from A-D):

A) Ligand Gated Ion Channels Receptor Types A) Ligand Gated Ion Channels

A) Ligand Gated Ion Channels Receptor Types A) Ligand Gated Ion Channels This family of receptors is responsible for regulation of the flow of ions across cell membranes The activity of these channels is regulated by the binding of a ligand to the channel Response to these receptors is very rapid (only a few milliseconds) Example: stimulation of the Nicotinic receptor by acetylcholine results in sodium influx, generation of an action potential, and activation of contraction in skeletal muscles

Receptor Types B) G-Protein-Coupled Receptors (GPCRs) G protein–coupled receptors are the most abundant type of receptors The extracellular domain of this receptor contains the ligand-binding area Intracellularly, these receptors are linked to a G protein (Gs, Gi, and others) having three subunits, an α subunit that binds guanosine Diphosphate (GDP) and a β-γ subunit Binding of the appropriate ligand to the extracellular region of the receptor activates the G protein so that GTP replaces guanosine diphosphate (GDP) on the α subunit Dissociation of the G protein occurs, and the α-GTP subunit interact with other cellular effectors, usually an enzyme or an ion channel to give the biological effect Example: Adrenoceptors

Receptor types B) G-Protein-Coupled Receptors (GPCRs)

Receptor Types C) Enzyme-Linked Receptors  The binding of an extracellular ligand to this type of receptors causes enzymatic  activity on its intracellular side Metabolism, growth, and differentiation are important biological functions controlled by these types of receptors An example of enzyme-linked receptors is Insulin Receptors

Receptor Types C) Intracellular Receptors  The receptor is entirely intracellular. therefore, the ligand must diffuse inside the cell to interact with the receptor (The Drug should be ????? In order to pass through the cell membrane) Example : Steroid Hormones Receptors Ligand

Some Definitions When a drug binds to its receptor, It may have one of these effects: Agonist An agonist binds to a receptor and produces a biologic response. An agonist may mimic the response of the endogenous ligand on the receptor, or it may elicit a different response from the receptor PartialAgonist are drugs that bind to and activate a given receptor, but have only partial  efficacy at the receptor relative to a full agonist. They may also considered ligands which display both agonistic and antagonistic effects Antagonist Antagonists are drugs that decrease or oppose the actions of another drug or endogenous ligand. An antagonist has no effect if an agonist is not present. Antagonist may be Reversible or Irreversible

Some Definitions Two Factors that Determine the Binding of the Drug to its Receptor: Affinity The tendency of a drug to bind to the receptors Efficacy The tendency for the drug, once bound, to activate the receptor