Sympatholytic
Encyclopedia
A sympatholytic drug is a medication which inhibits the postganglionic functioning of the sympathetic nervous system
(SNS). They are indicated for various functions, for example they may be used as antihypertensive
s. They are also used to treat anxiety, such as Generalized Anxiety Disorder, Panic Disorder and PTSD.
and norepinephrine
. They are primarily adrenergic antagonist
s, (Alpha Blockers and Beta Blockers) inhibiting adrenergic receptor
s, but there are exceptions: clonidine
is an adrenergic agonist on the α2 receptor, since this receptor is located presynaptically to inhibit further release of adrenaline and noradrenaline.
Other ways of inhibiting adrenergic signaling is by catecholamine synthesis blocking, e.g. by methyltyrosine. Reserpine
works by inhibiting transport into synaptic vesicle
s of noradrenaline by inhibiting the VMAT.
s include:
In Anxiety
Beta Blockers
There is clear evidence from many controlled trials in the past 25 years that beta blockers are effective in anxiety disorders, though the mechanism of action is not known (2). Some people have used beta blockers for 'performance anxiety'. In particular, musicians, public speakers, actors, and professional dancers, have been known to use beta blockers to avoid stage fright and tremor during public performance and especially auditions. The physiological symptoms of the fight/flight response associated with performance anxiety and panic (pounding heart, cold/clammy hands, increased respiration, sweating, etc.) are significantly reduced, thus enabling anxious individuals to concentrate on the task at hand. Stutterers also use beta blockers to avoid fight/flight responses, hence reducing the tendency to stutter.
Since they promote a lower heart rate and reduce tremor, beta blockers have been used by some Olympic marksmen to enhance performance, though beta blockers are banned by the International Olympic Committee (IOC).[2] Although they have no recognisable benefit to most sports, it is acknowledged that they are beneficial to sports such as archery and shooting. A recent, high-profile transgression took place in the 2008 Summer Olympics, where 50 metre pistol silver medallist and 10 metre air pistol bronze medallist Kim Jong-su tested positive for propranolol and was stripped of his medal.
PTSD
Posttraumatic stress disorder (PTSD) is theorized to be the result of neurological patterns caused by adrenaline and fear in the brain. By administering beta blockers immediately following a traumatic event, as well as over the next couple weeks, the formation of PTSD has been reduced in clinical studies.[2]
Alpha Blockers
Alpha Blockers can also be used to treat anxiety and panic, such as Generalized Anxiety Disorder, Panic Disorder or PTSD. Alpha2-adrenergic receptor agonists, such as clonidine
and guanfacine
, act at noradrenergic autoreceptors to inhibit the firing of cells in the locus ceruleus, effectively reducing the release of brain norepinephrine
(3). Clonidine
has shown promise among patients with Anxiety, Panic and PTSD in clinical trials and was used to treat severely and chronically abused and neglected preschool children. It improved disturbed behavior by reducing aggression, impulsivity, emotional outbursts, and oppositionality (4). Insomnia and nightmares were also reported to be reduced.
Kinzie and Leung (5) prescribed the combination of clonidine
and imipramine
to severely traumatized Cambodian refugees with Anxiety, Panic and PTSD. Global symptoms of PTSD were reduced among sixty-six percent and nightmares among seventy-seven percent. Guanfacine
produces less sedation than clonidine
and thus may be better tolerated. Guanfacine
reduced the trauma-related nightmares (6). A recently completed randomized double-blind trial among veteran patients with chronic PTSD showed that augmentation with guanfacine
was associated with improvement in anxiety and PTSD.
Prazosin
is an alpha1-receptor antagonist. Raskin and colleagues (7) studied the efficacy of prazosin for PTSD among Vietnam combat veterans in a 20-week double-blind crossover protocol with a two-week drug washout to allow for return to baseline (7). The CAPS and the Clinical Global Impressions-Change scale (CGI-C) were the primary outcome measures. Patients who were taking prazosin
had a robust improvement in overall sleep quality (effect size, 1.6) and recurrent distressing dreams (effect size, 1.9). In each of the PTSD symptom clusters the effect size was medium to large: .7 for reexperiencing or intrusion, .6 for avoidance and numbing, and .9 for hyperarousal. The reduction in CGI-C scores (overall PTSD severity and function at endpoint) also reflected a large effect size (1.4). Prazosin appears to have promise as an effective treatment for PTSD-related sleep disturbance, including trauma-related nightmares, as well as overall Anxiety and PTSD symptoms.
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
(SNS). They are indicated for various functions, for example they may be used as antihypertensive
Antihypertensive
The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...
s. They are also used to treat anxiety, such as Generalized Anxiety Disorder, Panic Disorder and PTSD.
Antiadrenergic
Antiadrenergic agents inhibit the signals of epinephrineEpinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
. They are primarily adrenergic antagonist
Adrenergic antagonist
An Adrenergic antagonist is a pharmaceutical substance that acts to inhibit the action of the adrenergic receptors. It is thus a type of sympatholytic.It has the opposite effect as adrenergic agonists.More specifically, they can be divided into:...
s, (Alpha Blockers and Beta Blockers) inhibiting adrenergic receptor
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
s, but there are exceptions: clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
is an adrenergic agonist on the α2 receptor, since this receptor is located presynaptically to inhibit further release of adrenaline and noradrenaline.
Other ways of inhibiting adrenergic signaling is by catecholamine synthesis blocking, e.g. by methyltyrosine. Reserpine
Reserpine
Reserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...
works by inhibiting transport into synaptic vesicle
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
s of noradrenaline by inhibiting the VMAT.
In hypertension
Many antiadrenergic agents used as antihypertensiveAntihypertensive
The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...
s include:
- centrally acting:
- ClonidineClonidineClonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
(α2 agonist) - GuanfacineGuanfacineGuanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...
(α2 agonist) - MethyldopaMethyldopaMethyldopa is an alpha-adrenergic agonist psychoactive drug used as a sympatholytic or antihypertensive. Its use is now mostly deprecated following the introduction of alternative safer classes of agents...
(α2 agonist) - MoxonidineMoxonidineMoxonidine is a new generation centrally acting antihypertensive drug licensed for the treatment of mild to moderate essential hypertension. It may have a role when thiazides, beta-blockers, ACE inhibitors and calcium channel blockers are not appropriate or have failed to control blood pressure...
(imidazoline receptorImidazoline receptorImidazoline receptors are receptors for clonidine and other imidazolines.-Classes:There are three classes of imidazoline receptors:* I1 receptor – mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure, * I2 receptor – an allosteric binding site of monoamine oxidase and is...
agonist) - PrazosinPrazosinPrazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth...
(α1 antagonist) - RescinnamineRescinnamineRescinnamine is an angiotensin-converting enzyme inhibitor used as an antihypertensive drug.It is an alkaloid obtained from Rauwolfia serpentina and other species of Rauwolfia....
(ACE inhibitorACE inhibitorACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
) - ReserpineReserpineReserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...
(VMAT inhibitor) - RilmenidineRilmenidineRilmenidine is a prescription medication for the treatment of hypertension. It is marketed under the brand names HYPERIUM and Tenaxum.- Form and composition :...
(imidazoline receptorImidazoline receptorImidazoline receptors are receptors for clonidine and other imidazolines.-Classes:There are three classes of imidazoline receptors:* I1 receptor – mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure, * I2 receptor – an allosteric binding site of monoamine oxidase and is...
agonist)
- Clonidine
- ganglion-blockingGanglionic blockerA ganglionic blocker is a type of medication that inhibits postganglionic transmission, primarily by acting as a nicotinic antagonist....
- MecamylamineMecamylamineMecamylamine is a nonselective and noncompetitive antagonist of the nicotinic acetylcholine receptors that was introduced in the 1950s as an antihypertensive agent.- Uses :...
(α3β4 nicotinic receptor inhibitor) - TrimethaphanTrimethaphanTrimetaphan camsilate or trimethaphan camsylate , trade name Arfonad, is a drug that counteracts cholinergic transmission at the ganglion type of nicotinic receptors of the autonomic ganglia and therefore blocks both the sympathetic nervous system and the parasympathetic nervous system...
(ganglion type receptor inhibitor)
- Mecamylamine
- peripherally acting
- GuanethidineGuanethidineGuanethidine is an antihypertensive drug that reduces the release of catecholamines, such as norepinephrine. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself , and uptake is essential for the drug's action...
(Magnesium-ATPaseMagnesium-ATPaseMagnesium ATPase is an ATPase that pumps magnesium. It is found in erythrocytes. The antihypertensive medication guanethidine works by inhibiting it. It is encoded by the gene ....
inhibitor) - IndoraminIndoraminIndoramin is a piperidine antiadrenergic agent.It is an alpha-1 selective adrenoceptor antagonist. with direct myocardial depression action,therefore,it results in no reflex tachycardiaIt is commonly synthesized from tryptophol...
(α1 antagonist) - DoxazosinDoxazosinDoxazosin mesylate, a quinazoline compound sold by Pfizer under the brand names Cardura and Carduran, is an α1a-selective alpha blocker used to treat high blood pressure and urinary retention associated with benign prostatic hyperplasia ....
(alpha blockerAlpha blockerAlpha-1 blockers constitute a variety of drugs which block α1-adrenergic receptors in arteries and smooth muscles.-Pharmacology:...
)
- Guanethidine
- Beta Blocker
- Non-selective agents
- AlprenololAlprenololAlprenolol, or alfeprol, alpheprol, and alprenololum , is a non-selective beta blocker as well as 5-HT1A receptor antagonist, used in the treatment of angina pectoris...
- BucindololBucindololBucindolol is a non-selective beta blocker with additional weak alpha-blocking properties and some intrinsic sympathomimetic activity. It was under review by the FDA in the United States for the treatment of heart failure in 2009 ....
- CarteololCarteololCarteolol is a non-selective beta blocker used to treat glaucoma....
- CarvedilolCarvedilolCarvedilol is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure . It is marketed under various trade names including Carvil , Coreg , Dilatrend , Eucardic , and Carloc as a generic drug ., and as a...
(has additional α-blocking activity) - LabetalolLabetalolLabetalol is a mixed alpha/beta adrenergic antagonist, which is used to treat high blood pressure.-Indications:...
(has additional α-blocking activity) - NadololNadololNadolol is a non-selective beta blocker used in the treatment of high blood pressure, migraine headaches, and chest pain.-Pharmacology:...
- PenbutololPenbutololPenbutolol is a medication in the class of beta blockers, used in the treatment of high blood pressure.-External links:*...
(has intrinsic sympathomimetic activity) - PindololPindololPindolol is a beta blocker....
(has intrinsic sympathomimetic activity) - Propranolol
- SotalolSotalolSotalol is a drug used in individuals with rhythm disturbances of the heart, and to treat hypertension in some individuals. It is a non-selective competitive β-adrenergic receptor blocker that also exhibits Class III antiarrhythmic properties by its inhibition of potassium channels...
- TimololTimololTimolol maleate is a non-selective beta-adrenergic receptor blocker.-Uses:In its oral form , it is used:* to treat high blood pressure* to prevent heart attacks* to prevent migraine headaches...
- Alprenolol
- β1-Selective agents
- AcebutololAcebutololAcebutolol is a beta blocker for the treatment of hypertension and arrhythmias.-Pharmacology:Acebutolol is a cardioselective beta blocker with ISA...
(has intrinsic sympathomimetic activity) - Atenolol
- BetaxololBetaxololBetaxolol is a selective beta1 receptor blocker used in the treatment of hypertension and glaucoma. Being selective for beta1 receptors, it typically has fewer systemic side effects than non-selective beta-blockers, for example, not causing bronchospasm as timolol may...
- BisoprololBisoprololBisoprolol is a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases. More specifically, it is a selective type β1 adrenergic receptor blocker. The FDA approved Duramed Pharmaceutical's application for Zebeta Oral Tablets as a new molecular...
- CeliprololCeliprololCeliprolol is a medication in the class of beta blockers, used in the treatment of high blood pressure....
- EsmololEsmololEsmolol is a cardioselective beta1 receptor blocker with rapid onset, a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilising activity at therapeutic dosages....
[39] - MetoprololMetoprololMetoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate...
- NebivololNebivololNebivolol is a β1 receptor blocker with nitric oxide-potentiating vasodilatory effect used in treatment of hypertension and, in Europe, also for left ventricular failure...
- Acebutolol
- β2-Selective agents
- ButaxamineButaxamineButaxamine is a β2-selective beta blocker. Its primary use is in experimental situations in which blockade of β2 receptors is necessary to determine the activity of the drug...
(weak α-adrenergic agonist activity) - No common clinical applications, but used in experiments. - ICI-118,551 Highly selective β2-adrenergic receptor antagonist - No known clinical applications, but used in experiments due to its strong receptor specificity.
- Butaxamine
- Non-selective agents
In Anxiety
Beta Blockers
There is clear evidence from many controlled trials in the past 25 years that beta blockers are effective in anxiety disorders, though the mechanism of action is not known (2). Some people have used beta blockers for 'performance anxiety'. In particular, musicians, public speakers, actors, and professional dancers, have been known to use beta blockers to avoid stage fright and tremor during public performance and especially auditions. The physiological symptoms of the fight/flight response associated with performance anxiety and panic (pounding heart, cold/clammy hands, increased respiration, sweating, etc.) are significantly reduced, thus enabling anxious individuals to concentrate on the task at hand. Stutterers also use beta blockers to avoid fight/flight responses, hence reducing the tendency to stutter.
Since they promote a lower heart rate and reduce tremor, beta blockers have been used by some Olympic marksmen to enhance performance, though beta blockers are banned by the International Olympic Committee (IOC).[2] Although they have no recognisable benefit to most sports, it is acknowledged that they are beneficial to sports such as archery and shooting. A recent, high-profile transgression took place in the 2008 Summer Olympics, where 50 metre pistol silver medallist and 10 metre air pistol bronze medallist Kim Jong-su tested positive for propranolol and was stripped of his medal.
PTSD
Posttraumatic stress disorder (PTSD) is theorized to be the result of neurological patterns caused by adrenaline and fear in the brain. By administering beta blockers immediately following a traumatic event, as well as over the next couple weeks, the formation of PTSD has been reduced in clinical studies.[2]
Alpha Blockers
Alpha Blockers can also be used to treat anxiety and panic, such as Generalized Anxiety Disorder, Panic Disorder or PTSD. Alpha2-adrenergic receptor agonists, such as clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
and guanfacine
Guanfacine
Guanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...
, act at noradrenergic autoreceptors to inhibit the firing of cells in the locus ceruleus, effectively reducing the release of brain norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(3). Clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
has shown promise among patients with Anxiety, Panic and PTSD in clinical trials and was used to treat severely and chronically abused and neglected preschool children. It improved disturbed behavior by reducing aggression, impulsivity, emotional outbursts, and oppositionality (4). Insomnia and nightmares were also reported to be reduced.
Kinzie and Leung (5) prescribed the combination of clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
and imipramine
Imipramine
Imipramine , also known as melipramine, is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group...
to severely traumatized Cambodian refugees with Anxiety, Panic and PTSD. Global symptoms of PTSD were reduced among sixty-six percent and nightmares among seventy-seven percent. Guanfacine
Guanfacine
Guanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...
produces less sedation than clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
and thus may be better tolerated. Guanfacine
Guanfacine
Guanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...
reduced the trauma-related nightmares (6). A recently completed randomized double-blind trial among veteran patients with chronic PTSD showed that augmentation with guanfacine
Guanfacine
Guanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...
was associated with improvement in anxiety and PTSD.
Prazosin
Prazosin
Prazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth...
is an alpha1-receptor antagonist. Raskin and colleagues (7) studied the efficacy of prazosin for PTSD among Vietnam combat veterans in a 20-week double-blind crossover protocol with a two-week drug washout to allow for return to baseline (7). The CAPS and the Clinical Global Impressions-Change scale (CGI-C) were the primary outcome measures. Patients who were taking prazosin
Prazosin
Prazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth...
had a robust improvement in overall sleep quality (effect size, 1.6) and recurrent distressing dreams (effect size, 1.9). In each of the PTSD symptom clusters the effect size was medium to large: .7 for reexperiencing or intrusion, .6 for avoidance and numbing, and .9 for hyperarousal. The reduction in CGI-C scores (overall PTSD severity and function at endpoint) also reflected a large effect size (1.4). Prazosin appears to have promise as an effective treatment for PTSD-related sleep disturbance, including trauma-related nightmares, as well as overall Anxiety and PTSD symptoms.