A sympatholytic (or sympathoplegic) drug is a medication which inhibits the postganglionic functioning of the sympathetic nervous system (SNS).[1] They are indicated for various functions, for example they may be used as antihypertensives. They are also used to treat anxiety, such as Generalized Anxiety Disorder, Panic Disorder and PTSD.
Contents
- 1 Antiadrenergic
- 1.1 In hypertension
- 1.2 In Anxiety
- 1.2.1 Beta Blockers
- 1.2.2 Alpha Blockers
- 2 References
- 3 External links
Antiadrenergic
Antiadrenergic agents inhibit the signals of epinephrine and norepinephrine. They are primarily adrenergic antagonists, (Alpha Blockers and Beta Blockers) inhibiting adrenergic receptors, 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 vesicles of noradrenaline by inhibiting the VMAT.
In hypertension
Many antiadrenergic agents used as antihypertensives include:
- centrally acting:
- Prazosin (α1 antagonist)
- Rescinnamine (ACE inhibitor)
- Reserpine (VMAT inhibitor)
- Rilmenidine (imidazoline receptor agonist)
- ganglion-blocking
- Mecamylamine (α3β4 nicotinic receptor antagonist)
- Trimethaphan (ganglion type receptor antagonist)
- peripherally acting
- Guanethidine (Magnesium-ATPase inhibitor)
- Indoramin (α1 antagonist)
- Doxazosin (alpha blocker)
- Beta Blocker
- Non-selective agents
- Alprenolol
- Bucindolol
- Carteolol
- Carvedilol (has additional α-blocking activity)
- Labetalol (has additional α-blocking activity)
- Nadolol
- Penbutolol (has intrinsic sympathomimetic activity)
- Pindolol (has intrinsic sympathomimetic activity)
- Propranolol
- Sotalol
- Timolol
- β1-Selective agents
- Acebutolol (has intrinsic sympathomimetic activity)
- Atenolol
- Betaxolol
- Bisoprolol
- Celiprolol
- Esmolol
- Metoprolol
- Nebivolol
- β2-Selective agents
- Butaxamine (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.
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.
Post traumatic stress disorder (PTSD) is theorized to be the result of neurological patterns caused by adrenaline and fear in the brain. By administering beta blockers which can cross the blood brain barrier 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 prescribed the combination of clonidine and imipramine to severely traumatized Cambodian refugees with Anxiety, Panic and PTSD.[5] 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.[citation needed]
Prazosin is an alpha1-receptor antagonist. Raskind and colleagues 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. 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: 0.7 for reexperiencing or intrusion, and 0.6 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.[7]
References
- ^ "Dorlands Medical Dictionary:sympatholytic".
- ^ a b c Tyrer, Peter (January 1992). "Anxiolytics not acting at the benzodiazepine receptor: Beta blockers". Progress in Neuro-Psychopharmacology and Biological Psychiatry 16 (1): 17–26. doi:10.1016/0278-5846(92)90004-X. PMID 1348368.
- ^ Kaplan HI, Sadock B (1998). Kaplan and Sadock's Synopsis of Psychiatry (8th ed.). Baltimore: Lippincott Williams & Wilkins.
- ^ Robert J. Harmon; et al. (September 1996). "Clonidine for Posttraumatic Stress Disorder in Preschool Children". Journal of the American Academy of Child & Adolescent Psychiatry 35 (9): 1247–1249. doi:10.1097/00004583-199609000-00022.
- ^ Kinzie, J David; Leung, Paul (September 1989). "Clonidine in Cambodian Patients with Posttraumatic Stress Disorder". Journal of Nervous & Mental Disease 177 (9): 546–550. doi:10.1097/00005053-198909000-00005. PMID 2769247.
- ^ Horrigan, Joseph P.; Barnhill, L. Jarrett (Aug 1996). "The suppression of nightmares with guanfacine". Journal of Clinical Psychiatry 57 (8): 371.
- ^ Murray A. Raskind; et al. (February 2003). "Reduction of Nightmares and Other PTSD Symptoms in Combat Veterans by Prazosin: A Placebo-Controlled Study". The American Journal of Psychiatry 160 (2): 371–373. doi:10.1176/appi.ajp.160.2.371.
External links
- Sympatholytics at the US National Library of Medicine Medical Subject Headings (MeSH)
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Neuromodulation
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| Types |
- ♦ Enzyme: Inducer
- Inhibitor
- ♦ Ion channel: Opener
- Blocker
- ♦ Receptor: Agonist
- Partial agonist
- Antagonist
- Inverse agonist
- Positive allosteric modulator (PAM)
- Negative allosteric modulator (NAM)
- ♦ Transporter [Reuptake]: Enhancer (RE)
- Inhibitor (RI)
- Releaser (RA)
- ♦ Miscellaneous: Precursor
- Cofactor
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| Classes |
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Enzyme
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see Enzyme inhibition
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Ion channel
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- Calcium channel blocker (CCB)
- Potassium channel blocker (PCB)
- Sodium channel blocker (SCB)
- Potassium channel opener (PCO)
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Receptor &
transporter
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BA/M
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Adrenergic
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- Adrenergic receptor agonist (α
- β (1
- 2))
- Adrenergic receptor antagonist (α (1
- 2), β)
- Adrenergic reuptake inhibitor (ARI)
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Dopaminergic
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- Dopamine receptor agonist
- Dopamine receptor antagonist
- Dopamine reuptake inhibitor (DRI)
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Histaminergic
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- Histamine receptor agonist
- Histamine receptor antagonist (H1
- H2
- H3)
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Serotonergic
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- Serotonin receptor agonist
- Serotonin Receptor Antagonist (5-HT3)
- Serotonin reuptake inhibitor (SRI)
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AA
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GABAergic
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- GABA receptor agonist
- GABA receptor antagonist
- GABA reuptake inhibitor (GRI)
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Glutamatergic
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- Glutamate receptor agonist (AMPA)
- Glutamate receptor antagonist (NMDA)
- Glutamate reuptake inhibitor
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Cholinergic
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- Acetylcholine receptor agonist (Muscarinic
- Nicotinic)
- Acetylcholine receptor antagonist (Muscarinic
- Nicotinic (Ganglionic
- Muscular))
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Cannabinoidergic
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- Cannabinoid receptor agonist
- Cannabinoid receptor antagonist
- Endocannabinoid enhancer (eCBE)
- Endocannabinoid reuptake inhibitor (eCBRI)
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Opioidergic
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- Opioid modulator
- Opioid receptor agonist
- Opioid receptor antagonist
- Enkephalinase inhibitor
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Other
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- Adenosine reuptake inhibitor (AdoRI)
- Angiotensin II receptor antagonist
- Endothelin receptor antagonist
- NK1 receptor antagonist
- Vasopressin receptor antagonist
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Miscellaneous
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- Cofactor (see Enzyme cofactors)
- Precursor (see Amino acids)
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Sympatholytic (and closely related) antihypertensives (C02)
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Sympatholytics
(antagonize α-adrenergic
vasoconstriction) |
| Central |
| α2 agonist |
- Clonidine
- Guanabenz
- Guanfacine
- Methyldopa#
- Tiamenidine‡
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| Adrenergic release inhibitors |
- Bethanidine
- Bretylium
- Debrisoquine
- Guanadrel
- Guanazodine
- Guanethidine
- Guanoclor
- Guanazodine
- Guanoxabenz
- Guanoxan
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| Imidazoline receptor agonist |
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| Ganglion-blocking/nicotinic antagonist |
- Hexamethonium‡
- Mecamylamine
- Pentolinium
- Trimethaphan
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| Peripheral |
| Indirect |
| MAOI |
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| Adrenergic uptake inhibitor |
- Bietaserpine
- Deserpidine
- Methoserpidine
- Rescinnamine
- Reserpine
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| Tyrosine hydroxylase inhibitor |
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| Direct |
| α1 blockers |
- Prazosin
- Indoramin
- Trimazosin
- Doxazosin
- Urapidil
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| Non-selective α blocker |
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| Other antagonists |
| Serotonin antagonist |
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| Endothelin antagonist (for PH) |
- dual (Bosentan, Macitentan)
- selective (Ambrisentan, Sitaxentan)
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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