Tricyclic antidepressant: Difference between revisions
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In [[medicine]] and [[pharmacology]], '''tricyclic antidepressants''' are [[adrenergic uptake inhibitor]]s that "contain a fused three-ring moiety and are used in the treatment of [[depression]]. These drugs block the uptake of [[norepinephrine]] and [[serotonin]] into axon terminals and may block some subtypes of serotonin, adrenergic, and [[histamine]] receptors. However the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system."<ref>{{MeSH}}</ref> | In [[medicine]] and [[pharmacology]], '''tricyclic antidepressants''' are [[antidepressant]]s that are [[adrenergic uptake inhibitor]]s that "contain a fused three-ring moiety and are used in the treatment of [[depression]]. These drugs block the uptake of [[norepinephrine]] and [[serotonin]] into axon terminals and may block some subtypes of serotonin, adrenergic, and [[histamine]] receptors. However the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system."<ref>{{MeSH}}</ref> | ||
==Classification== | |||
===Tertiary amine tricyclics=== | |||
Older tricyclics include [[amitriptyline]], [[doxepin]], and [[imipramine]] have a tertiary-amine side chain block both [[serotonin]] and [[norepinephrine]] and increase [[parasympathetic nervous system|anticholinergic]] [[drug toxicity]].<ref name="isbn0-07-142280-3">{{cite book |author= |authorlink= |editor=Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Lazo, John S.; Gilman, Alfred |others= |title=Goodman & Gilman's The Pharmacological Basis of Therapeutics |edition=11th |chapter=Antidepressant Agents |chapterurl= |language= |publisher=McGraw-Hill |location=New York |year=2006 |origyear= |pages= |quote= |isbn=0-07-142280-3 |oclc= |doi= |url=http://www.accessmedicine.com/resourceTOC.aspx?resourceID=28 |accessdate=}}</ref> | |||
===Secondary amine tricyclics=== | |||
Secondary amine tricyclics include desipramine, nortriptyline, and others. These medications have less affect on [[serotonin receptor]]s and more on [[norepinephrine receptor]]s. These medications have less [[parasympathetic nervous system|anticholinergic]] [[drug toxicity]] and less sedation.<ref> Baldessarini Ross J, "[http://www.accessmedicine.com/content.aspx?aID=938748 Chapter 17. Drug Therapy of Depression and Anxiety Disorders]" (Chapter). Brunton LL, Lazo JS, Parker KL: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e</ref> | |||
===Tetracyclics=== | |||
[[Mirtazapine]], a tetracyclic compound, is classified as a tricyclic antidepressant by the [[National Library of Medicine]] in the [[United States of America|United States]].<ref>{{MeSH|Mirtazapine }}</ref> However, mirtazapine is also considered a [[second-generation antidepressant]]. | |||
==Mechanism of action== | |||
It is generally accepted that they antagonize [[catechol-O-methyl transferase]] in postsynaptic neurons. Blocking this enzyme means that it slows the metabolism of serotonin and norepinephrine in the postsynaptic neuron, keeping a higher concentration in the synapse that continues to affect receptors. In contrast, most second-generation antidepressants operate on the presynaptic neuron to maintain high synaptic levels of these neurotransmitters. | |||
[[Depression]] may be due to the monoamine-deficiency hypothesis, which is a "deficiency in [[serotonin]] or [[norepinephrine]] neurotransmission in the brain."<ref name="pmid18172175">{{cite journal |author=Belmaker RH, Agam G |title=Major depressive disorder |journal=N. Engl. J. Med. |volume=358 |issue=1 |pages=55–68 |year=2008 |pmid=18172175 |doi=10.1056/NEJMra073096|url=http://content.nejm.org/cgi/content/full/358/1/55}}</ref> | |||
By blocking the ''reuptake'' of [[norepinephrine]] and [[serotonin]], tricyclics may overcome the mono-amine deficiency.<ref name="isbn0-07-145153-6">{{cite book |author=Katzung, Bertram G. |authorlink= |editor= |others= |title=Basic and Clinical Pharmacology |edition=10th |chapter=Antidepressant Agents |chapterurl= |language= |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2006 |origyear= |pages= |quote= |isbn=0-07-145153-6 |oclc= |doi= |url=http://www.accessmedicine.com/resourceTOC.aspx?resourceID=16 |accessdate=}}</ref> | |||
==Medical uses== | |||
===Depression=== | |||
{{main|Depression}} | |||
===Irritable bowel=== | |||
{{main|Irritable bowel syndrome}} | |||
Tricyclic antidepressants can reduce symptoms of [[irritable bowel syndrome]], perhaps with greatest benefit for diarrhea-predominant irritable bowel syndrome.<ref>{{Cite journal | issn = 0002-9270 | volume = 104 | issue = S1 | pages = S1-S35 | title = An Evidence-Based Position Statement on the Management of Irritable Bowel Syndrome | journal = Am J Gastroenterol | accessdate = 2008-12-20 | date = 2008-12-18 | url = http://dx.doi.org/10.1038/ajg.2008.122 }}</ref> | |||
===Chronic pain=== | |||
{{main|Pain}} | |||
==Drug toxicity== | |||
[[Second-generation antidepressant]]s are not clearly safer than [[tricyclic antidepressant]]s.<ref name="pmid21810375">{{cite journal| author=Coupland CA, Dhiman P, Barton G, Morriss R, Arthur A, Sach T et al.| title=A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database. | journal=Health Technol Assess | year= 2011 | volume= 15 | issue= 28 | pages= 1-202, iii-iv | pmid=21810375 | doi=10.3310/hta15280 | pmc= | url= }} </ref> | |||
==References== | ==References== | ||
<references/> | <references/> | ||
Latest revision as of 14:32, 2 February 2023
In medicine and pharmacology, tricyclic antidepressants are antidepressants that are adrenergic uptake inhibitors that "contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system."[1]
Classification
Tertiary amine tricyclics
Older tricyclics include amitriptyline, doxepin, and imipramine have a tertiary-amine side chain block both serotonin and norepinephrine and increase anticholinergic drug toxicity.[2]
Secondary amine tricyclics
Secondary amine tricyclics include desipramine, nortriptyline, and others. These medications have less affect on serotonin receptors and more on norepinephrine receptors. These medications have less anticholinergic drug toxicity and less sedation.[3]
Tetracyclics
Mirtazapine, a tetracyclic compound, is classified as a tricyclic antidepressant by the National Library of Medicine in the United States.[4] However, mirtazapine is also considered a second-generation antidepressant.
Mechanism of action
It is generally accepted that they antagonize catechol-O-methyl transferase in postsynaptic neurons. Blocking this enzyme means that it slows the metabolism of serotonin and norepinephrine in the postsynaptic neuron, keeping a higher concentration in the synapse that continues to affect receptors. In contrast, most second-generation antidepressants operate on the presynaptic neuron to maintain high synaptic levels of these neurotransmitters.
Depression may be due to the monoamine-deficiency hypothesis, which is a "deficiency in serotonin or norepinephrine neurotransmission in the brain."[5]
By blocking the reuptake of norepinephrine and serotonin, tricyclics may overcome the mono-amine deficiency.[6]
Medical uses
Depression
Irritable bowel
Tricyclic antidepressants can reduce symptoms of irritable bowel syndrome, perhaps with greatest benefit for diarrhea-predominant irritable bowel syndrome.[7]
Chronic pain
Drug toxicity
Second-generation antidepressants are not clearly safer than tricyclic antidepressants.[8]
References
- ↑ Anonymous (2024), Tricyclic antidepressant (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ (2006) “Antidepressant Agents”, Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Lazo, John S.; Gilman, Alfred: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th. New York: McGraw-Hill. ISBN 0-07-142280-3.
- ↑ Baldessarini Ross J, "Chapter 17. Drug Therapy of Depression and Anxiety Disorders" (Chapter). Brunton LL, Lazo JS, Parker KL: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e
- ↑ Anonymous (2024), Mirtazapine (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Belmaker RH, Agam G (2008). "Major depressive disorder". N. Engl. J. Med. 358 (1): 55–68. DOI:10.1056/NEJMra073096. PMID 18172175. Research Blogging.
- ↑ Katzung, Bertram G. (2006). “Antidepressant Agents”, Basic and Clinical Pharmacology, 10th. New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-145153-6.
- ↑ (2008-12-18) "An Evidence-Based Position Statement on the Management of Irritable Bowel Syndrome". Am J Gastroenterol 104 (S1): S1-S35. ISSN 0002-9270. Retrieved on 2008-12-20.
- ↑ Coupland CA, Dhiman P, Barton G, Morriss R, Arthur A, Sach T et al. (2011). "A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database.". Health Technol Assess 15 (28): 1-202, iii-iv. DOI:10.3310/hta15280. PMID 21810375. Research Blogging.