Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in

heart rate Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excr ...

, force of cardiac contraction, and blood pressure. The primary endogenous agonists of the sympathetic nervous system are the catecholamines (i.e., epinephrine drenaline

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...

oradrenaline and dopamine), which function as both neurotransmitters and

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...

s. Sympathomimetic drugs are used to treat

cardiac arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and poss ...

and low blood pressure, or even delay

premature labor Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between ...

, among other things. These drugs can act through several mechanisms, such as directly activating

postsynaptic Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

, blocking breakdown and

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the Synapse, pre-synaptic neuron at a synapse) or glial cell after it has performed its function of ...

of certain neurotransmitters, or stimulating production and release of catecholamines.

Mechanisms of action

The mechanisms of sympathomimetic drugs can be direct-acting (direct interaction between drug and receptor), such as α-adrenergic agonists, β-adrenergic agonists, and

dopaminergic agonists A dopamine agonist (DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D2-like and D1-like, and they are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the ...

; or indirect-acting (interaction not between drug and receptor), such as

MAOI Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especia ...

COMT inhibitor A catechol-''O''-methyltransferase (COMT) inhibitor is a drug that inhibits the enzyme catechol-''O''-methyltransferase. This enzyme methylates catecholamines such as dopamine, norepinephrine and epinephrine. It also methylates levodopa. COMT in ...

s, release stimulants, and reuptake inhibitors that increase the levels of endogenous catecholamines.

Structure-activity relationship

For maximum sympathomimetic activity, a drug must have: # Amine group two carbons away from an aromatic group # A hydroxyl group at the chiral beta position in the R-configuration # Hydroxyl groups in the meta and para position of the aromatic ring to form a catechol which is essential for receptor binding The structure can be modified to alter binding. If the amine is primary or secondary, it will have direct action, but if the

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen Hydrogen is the chemical element wi ...

is tertiary, it will have poor direct action. Also, if the amine has bulky substituents, then it will have greater beta adrenergic receptor activity, but if the substituent is not bulky, then it will favor the alpha adrenergic receptors.

Direct-acting

Adrenergic receptor agonists

Direct stimulation of the α- and β- adrenergic receptors can produce sympathomimetic effects. Salbutamol is a widely used direct-acting β₂-agonist. Other examples include

phenylephrine Phenylephrine is a medication primarily used as a decongestant, to dilate the pupil, to increase blood pressure, and to relieve hemorrhoids. In the United States, it was previously used orally as an over-the-counter decongestant to relieve nas ...

isoproterenol Isoprenaline, or isoproterenol (brand name: Isoprenaline Macure), is a medication used for the treatment of bradycardia (slow heart rate), heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropyla ...

, and

dobutamine Dobutamine is a medication used in the treatment of cardiogenic shock (as a result of inadequate tissue perfusion) and severe heart failure. It may also be used in certain types of cardiac stress tests. It is given by IV only, as an injection in ...

Dopaminergic agonists

Stimulation of the D1 receptor by dopaminergic agonists such as

fenoldopam Fenoldopam mesylate (Corlopam) is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial agonist. Fenoldopam is used as an antihypertensive agent. It was approved by the Food and Drug Administration (FDA) in ...

is used intravenously to treat

hypertensive crisis Severely elevated blood pressure (equal to or greater than a systolic 180 or diastolic of 120—sometimes termed malignant or accelerated hypertension) is referred to as a hypertensive crisis, as blood pressure at this level confers a high risk ...

Indirect-acting

Dopaminergic stimulants such as amphetamine,

ephedrine Ephedrine is a central nervous system (CNS) stimulant that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in ...

, and

propylhexedrine Propylhexedrine, sold under the brand name Benzedrex, is a nasal decongestant, appetite suppressant, and psychostimulant medication. It is used medicinally for relief of congestion due to colds, allergies and allergic rhinitis. Propylhexedrin ...

work by causing the release of dopamine and norepinephrine, along with (in some cases) blocking the reuptake of these neurotransmitters.

Structure-activity relationship

A primary or secondary aliphatic amine separated by 2 carbons from a substituted benzene ring is minimally required for high agonist activity. The pKa of the amine is approximately 8.5-10. The presence of hydroxy group in the benzene ring at 3rd and 4th position shows maximum alpha- and beta-adrenergic activity.

Cross-reactivity

Illegal drugs The prohibition of drugs through sumptuary legislation or religious law is a common means of attempting to prevent the recreational use of certain intoxicating substances. While some drugs are illegal to possess, many governments regulate the ...

such as

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Ameri ...

and

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...

also affect dopamine, serotonin, and

. Norepinephrine is synthesized by the body from the amino acid tyrosine, and is used in the synthesis of epinephrine, which is a stimulating neurotransmitter of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

. Thus, all sympathomimetic amines fall into the larger group of stimulants (see

psychoactive drug A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. ...

chart). In addition to intended therapeutic use, many of these stimulants have

abuse potential Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...

, can induce tolerance, and possibly

physical dependence Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...

, although not by the same mechanism(s) as opioids or sedatives. The symptoms of physical withdrawal from stimulants can include fatigue, dysphoric mood, increased appetite, vivid or lucid dreams, hypersomnia or insomnia, increased movement or decreased movement, anxiety, and drug craving, as is apparent in the rebound withdrawal from certain

substituted amphetamines Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with sub ...

. Physical withdrawal from some sedatives can be potentially lethal, for instance

benzodiazepine withdrawal syndrome Benzodiazepine withdrawal syndrome often abbreviated to benzo withdrawal or BZD withdrawal is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines, either medically or recreationally develops a p ...

. Opioid withdrawal is very uncomfortable, often described as a bad case of the flu, with possibly severe abdominal cramps and diarrhoea as central symptoms, but it is rarely lethal unless the user has a comorbid condition. Sympathomimetic drugs are sometimes involved in development of cerebral vasculitis and generalized polyarteritis nodosa like diseases involving immune-complex deposition. Known reports of such hypersensitivity reactions include the use of pseudoephedrine, phenylpropanlolamine, methamphetamine and other drugs at prescribed doses as well as at over-doses.

Comparison

" Parasympatholytic" and "sympathomimetic" have similar effects, but through completely different pathways. For example, both cause mydriasis, but parasympatholytics reduce accommodation (

cycloplegia Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation. Because of the paralysis of the ciliary muscle, the curvature of the lens can no longer be adjusted to focus on nearby objects. This results in sim ...

) while sympathomimetics do not.

Examples

* amphetamine (Evekeo) *

benzylpiperazine Benzylpiperazine (BZP) is a recreational drug with euphoriant and stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. Adverse effects have been reported following its use including acute psychosis ...

(BZP) * cathine (found in '' Catha edulis'') * cathinone (found in '' Catha edulis'', khat) *

(found in ''

Erythroxylum coca ''Erythroxylum coca'' is one of two species of cultivated coca. Description The coca plant resembles a blackthorn bush, and grows to a height of . The branches are straight, and the leaves, which have a green tint, are thin, opaque, oval, and tap ...

'', coca) *

(found in ''

Ephedra Ephedra may refer to: * Ephedra (medicine), a medicinal preparation from the plant ''Ephedra sinica'' * ''Ephedra'' (plant), genus of gymnosperm shrubs See also * Ephedrine Ephedrine is a central nervous system (CNS) stimulant that is of ...

'') *

lisdexamfetamine Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eati ...

(Vyvanse) *

maprotiline Maprotiline, sold under the brand name Ludiomil among others, is a tetracyclic antidepressant (TeCA) that is used in the treatment of depression. It may alternatively be classified as a tricyclic antidepressant (TCA), specifically a secondary am ...

(Ludiomil) *

(Ecstasy, Molly) * methamphetamine (Meth, Crank, Desoxyn) *

methcathinone Methcathinone (α-methylamino- propiophenone or ephedrone) (sometimes called "cat" or "jeff" or "catnip" or "M-Kat" or "kat" or "intash" ) is a monoamine alkaloid and psychoactive stimulant, a substituted cathinone. It is used as a recreationa ...

methylenedioxypyrovalerone Methylenedioxypyrovalerone (MDPV) is a stimulant of the cathinone class that acts as a norepinephrine–dopamine reuptake inhibitor (NDRI). It was first developed in the 1960s by a team at Boehringer Ingelheim. Its activity at the dopamine tra ...

(MDPV) *

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser exten ...

(Ritalin) *

4-methylaminorex 4-Methylaminorex (4-MAR, 4-MAX) is a stimulant drug of the 2-amino-5-aryloxazoline class that was first synthesized in 1960 by McNeil Laboratories. It is also known by its street name "U4Euh" ("Euphoria"). It is banned in many countries as a s ...

oxymetazoline Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eyedrops to treat eye rednes ...

( Afrin,

Vicks Sinex Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eyedrops to treat eye redness d ...

) *

pemoline Pemoline, sold under the brand name Cylert among others, is a stimulant medication which has been used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It has been discontinued in most countries to due to rare ...

(Cylert) *

phenmetrazine Phenmetrazine ( INN, USAN, BAN) (brand name Preludin, and many others) is a stimulant drug first synthesized in 1952 and originally used as an appetite suppressant, but withdrawn from the market in the 1980s due to widespread abuse. It was initi ...

(Preludin) *

(Benzedrex) * pseudoephedrine (Sudafed, SudoGest, also found in ''Ephedra'' species) Benzphetamine (Didrex)

References

External links

* {{DEFAULTSORT:Sympathomimetic Drug