Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of
endogenous
Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell.
In contrast, exogenous substances and processes are those that originate from outside of an organism.
For example, es ...
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
s of the
sympathetic nervous system
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...
. 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
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
.
The primary endogenous agonists of the sympathetic nervous system are the
catecholamines
A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine.
Catechol can be either a free molecule or a substi ...
(i.e.,
epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
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
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
), which function as both
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
s 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 required ...
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 possib ...
and low
blood pressure
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
, 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 2 ...
, 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 sys ...
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 pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transm ...
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, especi ...
s,
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 atoms have been replaced by a substituen ...
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 receptor
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...
s can produce sympathomimetic effects.
Salbutamol
Salbutamol, also known as albuterol and sold under the brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist which works by causing rel ...
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 isopropylam ...
, 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 ...
.
Dopaminergic agonists
Stimulation of the
D1 receptor
Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family - receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.
Tissue distribution
D1 receptors are the most abundant kind of do ...
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 S ...
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
Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
,
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 Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
and
MDMA
3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
also affect
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
,
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
, and
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'', ...
.
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 par ...
. Thus, all sympathomimetic amines fall into the larger group of
stimulant
Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
s (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
Tolerance or toleration is the state of tolerating, or putting up with, conditionally.
Economics, business, and politics
* Toleration Party, a historic political party active in Connecticut
* Tolerant Systems, the former name of Veritas Software ...
, 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
Pseudoephedrine (PSE) is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent in higher doses.
It was first characteri ...
,
phenylpropanlolamine,
methamphetamine
Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...
and other drugs at prescribed doses as well as at over-doses.
Comparison
"
Parasympatholytic A parasympatholytic agent is a substance or activity that reduces the activity of the parasympathetic nervous system. (The parasympathetic nervous system is often colloquially described as the "Feed and Breed" or "Rest and Digest" portion of the a ...
" and "sympathomimetic" have similar effects, but through completely different pathways. For example, both cause
mydriasis
Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs.
Normally, as ...
, 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
Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
(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
-norpseudoephedrine, also known as cathine and (+)-norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which acts as a stimulant. Along with cathinone, it is found naturally in '' Catha edulis'' (kha ...
(found in ''
Catha edulis
Khat or qat ( ''ch’at''; Oromo: ''Jimaa'', so, qaad, khaad, khat or chat, ar, القات ''al-qāt'') is a flowering plant native to eastern and southern Africa. Khat contains the alkaloid cathinone, a stimulant, which is said to cause e ...
'')
*
cathinone
Cathinone (also known as benzoylethanamine, or β-keto-amphetamine) is a monoamine alkaloid found in the shrub '' Catha edulis'' (khat) and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the m ...
(found in ''
Catha edulis
Khat or qat ( ''ch’at''; Oromo: ''Jimaa'', so, qaad, khaad, khat or chat, ar, القات ''al-qāt'') is a flowering plant native to eastern and southern Africa. Khat contains the alkaloid cathinone, a stimulant, which is said to cause e ...
'', khat)
*
cocaine
Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
(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)
*
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 ...
(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 eating ...
(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)
*
MDMA
3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
(Ecstasy, Molly)
*
methamphetamine
Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...
(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 recreational ...
*
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 tr ...
(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 extent, ...
(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 redness d ...
(
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 b ...
(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 initia ...
(Preludin)
*
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 ...
(Benzedrex)
*
pseudoephedrine
Pseudoephedrine (PSE) is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent in higher doses.
It was first characteri ...
(Sudafed, SudoGest, also found in ''Ephedra'' species)
Benzphetamine (Didrex)
See also
*
Adrenergic storm
An adrenergic storm is a sudden and dramatic increase in serum levels of the catecholamines adrenaline and noradrenaline (also known as epinephrine and norepinephrine respectively), with a less significant increase in dopamine transmission. It ...
*
Sympathetic nervous system
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...
*
Sympatholytic A sympatholytic (or sympathoplegic) drug is a medication that opposes the downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system (SNS). They are indicated for various functions; for example, ...
References
External links
*
{{DEFAULTSORT:Sympathomimetic Drug