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, ...

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 ...

. 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 e ...

force of cardiac contraction Myocardial contractility represents the innate ability of the heart muscle (cardiac muscle or myocardium) to contract. The ability to produce changes in force during contraction result from incremental degrees of binding between different types of t ...

, 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 pressur ...

. 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 subst ...

(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 chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 8 ...

), 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. Neur ...

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

, 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, 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 trans ...

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, espec ...

s, COMT inhibitors, 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 substituent su ...

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 na ...

, isoproterenol, and dobutamine.

Dopaminergic agonists

Stimulation of the D1 receptor by dopaminergic agonists such as fenoldopam 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 n ...

, and propylhexedrine 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 th ...

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 Am ...

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 desired ...

also affect

, 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

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. T ...

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

, 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 s ...

. 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 phys ...

. 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 charac ...

, 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. Meth ...

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 aut ...

" 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, a ...

, but parasympatholytics reduce accommodation ( cycloplegia) while sympathomimetics do not.

Examples

(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 ''

'', khat) *

(found in '' Erythroxylum coca'', coca) *

(found in '' Ephedra'') * lisdexamfetamine (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 ...

(Ludiomil) *

(Ecstasy, Molly) *

(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 recreation ...

* methylenedioxypyrovalerone (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 st ...

* oxymetazoline ( Afrin, Vicks Sinex) * pemoline (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 (Benzedrex) *

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

References

External links

* {{DEFAULTSORT:Sympathomimetic Drug

Mechanisms of action

Structure-activity relationship

Direct-acting

Adrenergic receptor agonists

Dopaminergic agonists

Indirect-acting

Structure-activity relationship

Cross-reactivity

Comparison

Examples

See also

References

External links