Find information on medical topics, symptoms, drugs, procedures, news and more, written in everyday language.

Site Selectivity

by Angela Cafiero Moroney, PharmD

After being swallowed, injected, inhaled, or absorbed through the skin, most drugs enter the bloodstream and circulate throughout the body. Some drugs are given directly to the area where they are wanted. For example, eye drops are put directly in to the eyes. The drugs then interact with cells or tissues where they produce their intended effects (target sites). This interaction is called selectivity. Selectivity is the degree to which a drug acts on a given site relative to other sites. Some drugs are relatively nonselective. They affect many different tissues or organs. For example, atropine, a drug given to relax muscles in the digestive tract, may also relax muscles in the eyes and in the respiratory tract. Other drugs are relatively selective. For example, nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen (see Nonopioid Analgesics), target any area where inflammation is present. Still other drugs are highly selective. They affect mainly a single organ or system. For example, digoxin, a drug given to manage heart failure, affects mainly the heart, increasing its pumping efficiency. Sleep aids target certain nerve cells of the brain.

How do drugs know where to exert their effects? The answer involves how they interact with cells or substances such as enzymes.

Receptors on Cells

On their surface, most cells have many different types of receptors. A receptor is a molecule with a specific three-dimensional structure, which allows only substances that fit precisely to attach to it—as a key fits in its lock.

Receptors enable natural (originating in the body) substances outside the cell to influence the activity of the cell. Examples of such substances include neurotransmitters (chemicals that conduct messages between cells in the nervous system) and hormones (chemicals released into the bloodstream by one organ to affect another organ). That influence may be to stimulate or inhibit a process inside the cell. Drugs tend to mimic these natural substances and thus use receptors in the same way. For example, morphine and related pain-relieving drugs act on or affect the same receptors in the brain used by endorphins, which are substances produced by the body to help control pain.

Some drugs attach to only one type of receptor. Other drugs, like a master key, can attach to several types of receptors throughout the body. A drug’s selectivity can often be explained by how selectively it attaches to receptors.

A Perfect Fit

A receptor on the cell’s surface has a three-dimensional structure that allows a specific substance, such as a drug, hormone, or neurotransmitter, to bind to it because the substance also has a three-dimensional structure that perfectly fits the receptor, as a key fits a lock.

Agonists and antagonists

Drugs that target receptors are classified as agonists or antagonists. Agonist drugs activate, or stimulate, their receptors, triggering a response that increases or decreases the cell’s activity. Antagonist drugs block the access or attachment of the body’s natural agonists, usually neurotransmitters, to their receptors and thereby prevent or reduce cell responses to natural agonists.

Agonist and antagonist drugs can be used together in patients with asthma. For example, albuterol can be used with ipratropium. Albuterol, an agonist, attaches to specific (adrenergic) receptors on cells in the respiratory tract, causing relaxation of smooth muscle cells and thus widening of the airways (bronchodilation). Ipratropium, an antagonist, attaches to other (cholinergic) receptors, blocking the attachment of acetylcholine, a neurotransmitter that causes contraction of smooth muscle cells and thus narrowing of the airways (bronchoconstriction). Both drugs widen the airways (and make breathing easier) but in different ways.

Beta-blockers, such as propranolol, are a widely used group of antagonists. These drugs are used to treat high blood pressure, angina (chest pain caused by an inadequate blood supply to the heart muscle), and certain abnormal heart rhythms and to prevent migraines. They block or reduce stimulation of the heart by the agonist neurotransmitters epinephrine (adrenaline) and norepinephrine (noradrenaline), which are released during stress. Antagonists such as beta-blockers are most effective when the concentration of the agonist is high in a specific part of the body. Similar to the way a roadblock stops more vehicles during the 5:00 pm rush hour than at 3:00 am , beta-blockers, given in doses that have little effect on normal heart function, may have a greater effect during sudden surges of hormones released during stress and thereby protect the heart from excess stimulation.

Targets in The Body: Cell Receptors

Certain natural substances in the body, such as neurotransmitters and hormones, target specific receptors on the surface of cells. When these substances bind with the receptor on a cell, they stimulate that receptor to perform its function, which is to produce or to inhibit a specific action in the cell. Drugs can also target and bind with these receptors.

Some drugs act as agonists, stimulating the receptor in the same way that the body’s natural substances do. Others act as antagonists, blocking the action of the natural substance on the receptor. Each type of receptor has many subtypes, and drugs may act on one or several subtypes of receptors.

Type of Receptor

Body’s Natural Agonist

Resulting Action

Drugs That Target the Receptor

Adrenergic

Alpha 1

Epinephrine and norepinephrine

“Fight-or-flight” reactions: Constriction of the blood vessels in the skin, digestive tract, and urinary tract

Breakdown of glucose in the liver (releasing energy)

Decrease in activity of the stomach and intestines

Contraction of smooth muscle in the genital and urinary organs

Agonist: Methoxamine and phenylephrine

Antagonist: Doxazosin, prazosin, tamsulosin, and terazosin

Alpha 2

Epinephrine and norepinephrine

A decrease in insulin secretion, in the clumping of platelets, in the constriction of blood vessels in the skin and intestines, and in the release of norepinephrine from nerves

Agonist: Clonidine

Antagonist: Yohimbine

Beta 1

Epinephrine and norepinephrine

An increase in heart rate, in the force of heart contraction, and in secretion of renin (a hormone involved in controlling blood pressure)

Agonist: Dobutamine and isoproterenol

Antagonist: Beta-blockers (used to treat hypertension and heart disease), such as atenolol and metoprolol

Beta 2

Epinephrine and norepinephrine

Dilation of smooth muscle in the blood vessels, airways, digestive tract, and urinary tract

Breakdown of glycogen in skeletal muscles (releasing glucose for energy)

Agonist: Albuterol, isoetharine, and terbutaline

Antagonist: Propranolol

Cholinergic

Muscarinic

Acetylcholine

A decrease in heart rate and the force of the heart’s contraction

Constriction of airways

Dilation of blood vessels throughout the body

Increase in activity of the stomach, intestines, bladder, and salivary, lacrimal, and sweat glands

Agonist: Bethanechol and carbachol

Antagonist: Atropine, ipratropium, and scopolamine

Nicotinic

Acetylcholine

Contraction of skeletal muscles

Agonist: None commonly used

Antagonist: Atracurium, pancuronium, and tubocurarine

Histaminergic

H 1

Histamine

Production of an allergic response

Contraction of muscles in the airways and digestive tract

Dilation of small blood vessels

Drowsiness (sedation)

Agonist: None commonly used

Antagonist: Cetirizine, chlorpheniramine, clemastine, diphenhydramine, fexofenadine, and loratadine

H 2

Histamine

Stimulation of stomach secretions

Agonist: None commonly used

Antagonist: Cimetidine, famotidine, nizatidine, and ranitidine

Serotoninergic

Serotonin

Constriction of blood vessels within the brain

Stimulation of activity (motility) in the digestive tract

Contraction of blood vessels

Effects on sleep, memory, sensory perception, temperature regulation, mood, appetite, and hormone secretion

Partial agonist: Buspirone

Agonist*: Sumitriptan and zolmitriptan

Antagonist: Methysergide and ondansetron

Dopaminergic

Dopamine

Involvement in movement, mood, thinking, learning, and reward-seeking

Also increases blood flow to the kidneys, which allows for increased urine excretion

Agonist: Pramipexole and ropinirole

Antagonist: Olanzapine and risperidone

*Antidepressants called selective serotonin reuptake inhibitors (SSRIs) act by enhancing the effects of serotonin but are not agonists (they do not act on the serotonin receptor).


Enzymes

Instead of receptors, some drugs target enzymes, which regulate the rate of chemical reactions. Drugs that target enzymes are classified as inhibitors or activators (inducers). For example, the cholesterol-lowering drug lovastatin inhibits an enzyme called HMG-CoA reductase, which is critical in the body’s production of cholesterol. A side effect of the antibiotic rifampin is the activation of the enzymes involved in metabolizing oral contraceptives. When women who are taking an oral contraceptive also take rifampin, the contraceptive is metabolized (that is, broken down into inactive components) and removed from the body more quickly than usual and may therefore be ineffective.

Resources In This Article

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • LANOXIN
  • ATROPEN
  • ADVIL, MOTRIN IB
  • No US brand name
  • DURAMORPH PF, MS CONTIN
  • ISUPREL
  • DUVOID, URECHOLINE
  • ADRENALIN
  • LEVOPHED
  • AXID
  • ZANTAC
  • ALLEGRA
  • INDERAL
  • TAVIST-1
  • FLOMAX
  • PEPCID
  • ZOFRAN
  • MINIPRESS
  • MIRAPEX
  • CARDURA
  • TENORMIN
  • CATAPRES
  • RISPERDAL
  • HYTRIN
  • CHLOR-TRIMETON
  • MIOSTAT
  • ZOMIG
  • ATROVENT
  • PROVENTIL-HFA, VENTOLIN-HFA
  • TRANSDERM SCOP
  • ZYPREXA
  • ZYRTEC
  • REQUIP
  • LOPRESSOR, TOPROL-XL
  • ALAVERT, CLARITIN
  • TAGAMET
  • No US brand nameb
  • ALTOPREV
  • RIFADIN, RIMACTANE