Mirtazapine: Difference between revisions

Line 12:

==Chemistry==

Mirtazapine is a ~~tertrahedric~~ molecule of the piperazino-azepine and [[phenethylamine]] group of compounds. It is comprised of a fusion of pyridine, benzene, azepine, and piperazine rings. ~~Mirtazapine~~ is a tetracyclic antidepressant, named so because of their four-ring structure.

Mirtazapine is a synthetic tetrahedral molecule of the piperazino-azepine and [[phenethylamine]] group of compounds. It is comprised of a fusion of pyridine, benzene, azepine, and piperazine rings. It is a tetracyclic antidepressant, named so because of their four-ring structure. Mirtazapine is the 6-aza analog of mianserin, which is pharmacologically similar in function.

Mirtazapine is ~~the 6~~-~~aza analog~~ of ~~mianserin, which is pharmacologically similar in function~~.

Mirtazapine enhances central adrenergic and serotonergic transmission, possibly by acting as an antagonist at central presynaptic alpha 2 adrenergic inhibitory autoreceptors and heteroreceptors. This agent is a potent antagonist of 5-hydroxytryptamine type 2 (5-HT2), 5-HT3, and histamine 1 (H1) receptors, and a moderate antagonist of peripheral alpha 1 adrenergic and muscarinic receptors.<ref>NCl Thesaurus - Mirtazapine (Code C29265) https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C29265</ref>

==Pharmacology==

Mirtazapine acts as an [[antagonist]]/inverse agonist upon the following receptors:<ref>Discovery of New Tetracyclic Tetrahydrofuran Derivatives as Potential Broad-Spectrum Psychotropic Agents | http://pubs.acs.org/doi/abs/10.1021/jm049632c</ref><ref>Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, org 3770 and its enantiomers (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/0028390888901499</ref>

*[[serotonin|5-HT2A receptor]]<ref name="discovery">Fernández J, Alonso JM, Andrés JI, Cid JM, Díaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA. (2005)

Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents.

Line 35:

Line 36:

*H1 receptor<ref>Synthesis and Pharmacological Testing of 1,2,3,4,10,14b-Hexahydro-6-methoxy-2-methyldibenzo[c,f]pyrazino[1,2-a]azepin and Its Enantiomers in Comparison with the Two Antidepressants Mianserin and Mirtazapine | http://pubs.acs.org/doi/abs/10.1021/jm010566d</ref>

*[[acetylcholine|mACH receptors]]<ref>Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (in English) (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8</ref>

While mirtazapine has some affinity for the 5-HT2A receptor, it acts as an [[antagonist]]<ref> A Review of the Pharmacological and Clinical Profile of Mirtazapine http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2001.tb00198.x/epdf </ref> thus it is unlikely that this mechanism is responsible for its [[psychedelic]] and [[deliriant]] effects.

Additionally, Mirtazapine has also been observed to indirectly agonize the following GCPR in humans:

*[[Opioid]] receptor κ3<ref>Schreiber, S., Rigai, T., Katz, Y., & Pick, C. G. (2002). The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms. Brain research bulletin, 58(6), 601-605.</ref>

Line 46:

Line 49:

Clin Neuropharmacol, 19: 451-456. [PMID:8889289]</ref><ref>Rimoy GH, Wright DM, Bhaskar NK, Rubin PC. (1994)

The cardiovascular and central nervous system effects in the human of U-62066E. A selective opioid receptor agonist.

Eur J Clin Pharmacol, 46: 203-207. [PMID:8070500] </ref>. This even may explain mirtazapine's withdrawal/discontinuation effects as well as its promotion of ~~diurensis~~ and a possible increase in food intake (usually resulting in weight gain).

Eur J Clin Pharmacol, 46: 203-207. [PMID:8070500] </ref>. This even may explain mirtazapine's withdrawal/discontinuation effects as well as its promotion of diuresis and a possible increase in food intake (usually resulting in weight gain).

It should be noted that although some of these effects are observed in those who take mirtazapine recreationally (or one off dosing) most neurophysiological effects are observed in those with on-going use (15, 30 and 45 mg daily prescribed for depression, etc) due to a maintained level of mirtazapine in the body.

It ~~should be noted that although some~~ of ~~these effects are observed in those who take~~ mirtazapine ~~recreationally~~ (~~or one off dosing~~) ~~most neurophysiological effects are observed~~ in ~~those with on~~-~~going use~~ (15, ~~30 and 45mg daily prescribed for depression~~, ~~etc~~) ~~due to a maintained level~~ of ~~mirtazapine in the body~~.

The oral bioavailability of mirtazapine is about 50%. It is found mostly bound to plasma proteins, about 85%. It is metabolized primarily in the liver by demethylation and hydroxylation via cytochrome P450 enzymes, CYP1A2, CYP2D6, CYP3A4.<ref>Anttila, SA; Leinonen, EV (2001). "A review of the pharmacological and clinical profile of mirtazapine". ''CNS Drug Reviews''. '''7''' (3): 249–64. doi:10.1111/j.1527-3458.2001.tb00198.x. PMC 6494141. <nowiki>PMID 11607047</nowiki>.</ref> One of its major metabolites is desmethylmirtazapine. The overall elimination half-life is 20–40 hours. It is conjugated in the kidney for excretion in the urine, where 75% of the drug is excreted,<ref>Al-Majed, Abdulrahman; Bakheit, Ahmed H.; Alharbi, Raed M.; Abdel Aziz, Hatem A. (1 January 2018). ''Chapter Two - Mirtazapine''. ''Profiles of Drug Substances, Excipients and Related Methodology''. '''43'''. pp. 209–254. doi:10.1016/bs.podrm.2018.01.002. ISBN <bdi>9780128151259</bdi>. <nowiki>PMID 29678261</nowiki>.</ref> and about 15% is eliminated in feces.<ref>Schatzberg, Alan F. (2009). "Chapter 21: Mirtazapine". In Schatzberg, Alan F.; Nemeroff, Charles B. (eds.). ''The American Psychiatric Publishing Textbook of Psychopharmacology'' (4th ed.). Washington, D.C.: American Psychiatric Pub. ISBN <bdi>9781585623099</bdi>.</ref>

==Subjective effects==

Line 117:

Line 122:

===Combination effects===

*'''[[Cannabis]]''' - When mirtazapine is combined with cannabis, the euphoric and visual effects are greatly potentiated.

*'''[[Psychedelics]]''' - Due to mirtazapines action as a 5-HT2A antagonist, it can help reduce the intensity or "abort" a [[bad trip]]

Line 124:

Line 130:

{{#ask: [[Category:Mirtazapine]][[Category:Experience]]|format=ul|Columns=1}}

Additional experience reports can be found here:

* [https://www.erowid.org/experiences/subs/exp_Pharms_Mirtazapine.shtml Erowid Experience Vaults: Mirtazapine]

*[https://www.erowid.org/experiences/subs/exp_Pharms_Mirtazapine.shtml Erowid Experience Vaults: Mirtazapine]

==Toxicity and harm potential==

Line 144:

Line 151:

===Dangerous interactions===

**'''[[UncertainInteraction::Antidepressants]]''' - Different types of antidepressants can cause adverse effects as well as possible [[serotonin syndrome]] when mixed.

Line 155:

Line 163:

==See also==

*[[Responsible use]]

*[[Hallucinogen]]

Line 161:

Line 170:

==External links==

*[http://en.wikipedia.org/wiki/Mirtazapine Mirtazapine (Wikipedia)]

*[http://www.erowid.org/pharms/mirtazapine/mirtazapine.shtml Mirtazapine (Erowid Vault)]

*[https://isomerdesign.com/PiHKAL/explore.php?domain=pk&id=9430 Mirtazapine (Isomer Design)]

*[http://www.drugs.com/mirtazapine.html Mirtazapine (Drugs.com)]

===Discussion===

*[http://disregardeverythingisay.com/post/43240860676/mirtazapine-broken-down-and-described Mirtazapine, broken down and described (Disregard Everything I Say)]

@@ Line 12: / Line 12: @@
 ==Chemistry==
-Mirtazapine is a tertrahedric molecule of the piperazino-azepine and [[phenethylamine]] group of compounds. It is comprised of a fusion of pyridine, benzene, azepine, and piperazine rings. Mirtazapine is a tetracyclic antidepressant, named so because of their four-ring structure.
+Mirtazapine is a synthetic tetrahedral molecule of the piperazino-azepine and [[phenethylamine]] group of compounds. It is comprised of a fusion of pyridine, benzene, azepine, and piperazine rings. It is a tetracyclic antidepressant, named so because of their four-ring structure. Mirtazapine is the 6-aza analog of mianserin, which is pharmacologically similar in function.
-Mirtazapine is the 6-aza analog of mianserin, which is pharmacologically similar in function.
+Mirtazapine enhances central adrenergic and serotonergic transmission, possibly by acting as an antagonist at central presynaptic alpha 2 adrenergic inhibitory autoreceptors and heteroreceptors. This agent is a potent antagonist of 5-hydroxytryptamine type 2 (5-HT2), 5-HT3, and histamine 1 (H1) receptors, and a moderate antagonist of peripheral alpha 1 adrenergic and muscarinic receptors.<ref>NCl Thesaurus - Mirtazapine (Code C29265) https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C29265</ref>
 ==Pharmacology==
 Mirtazapine acts as an [[antagonist]]/inverse agonist upon the following receptors:<ref>Discovery of New Tetracyclic Tetrahydrofuran Derivatives as Potential Broad-Spectrum Psychotropic Agents | http://pubs.acs.org/doi/abs/10.1021/jm049632c</ref><ref>Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, org 3770 and its enantiomers (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/0028390888901499</ref>
 *[[serotonin|5-HT<sub>2A</sub> receptor]]<ref name="discovery">Fernández J, Alonso JM, Andrés JI, Cid JM, Díaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA. (2005)
 Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents.
@@ Line 35: / Line 36: @@
 *H<sub>1</sub> receptor<ref>Synthesis and Pharmacological Testing of 1,2,3,4,10,14b-Hexahydro-6-methoxy-2-methyldibenzo[c,f]pyrazino[1,2-a]azepin and Its Enantiomers in Comparison with the Two Antidepressants Mianserin and Mirtazapine | http://pubs.acs.org/doi/abs/10.1021/jm010566d</ref>
 *[[acetylcholine|mACH receptors]]<ref>Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (in English) (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8</ref>
 While mirtazapine has some affinity for the 5-HT<sub>2A</sub> receptor, it acts as an [[antagonist]]<ref> A Review of the Pharmacological and Clinical Profile of Mirtazapine http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2001.tb00198.x/epdf </ref> thus it is unlikely that this mechanism is responsible for its [[psychedelic]] and [[deliriant]] effects.
 Additionally, Mirtazapine has also been observed to indirectly agonize the following GCPR in humans:
 *[[Opioid]] receptor κ<sub>3</sub><ref>Schreiber, S., Rigai, T., Katz, Y., & Pick, C. G. (2002). The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms. Brain research bulletin, 58(6), 601-605.</ref>
@@ Line 46: / Line 49: @@
 Clin Neuropharmacol, 19: 451-456. [PMID:8889289]</ref><ref>Rimoy GH, Wright DM, Bhaskar NK, Rubin PC. (1994)
 The cardiovascular and central nervous system effects in the human of U-62066E. A selective opioid receptor agonist.
-Eur J Clin Pharmacol, 46: 203-207. [PMID:8070500] </ref>. This even may explain mirtazapine's withdrawal/discontinuation effects as well as its promotion of diurensis and a possible increase in food intake (usually resulting in weight gain).
+Eur J Clin Pharmacol, 46: 203-207. [PMID:8070500] </ref>. This even may explain mirtazapine's withdrawal/discontinuation effects as well as its promotion of diuresis and a possible increase in food intake (usually resulting in weight gain).
+It should be noted that although some of these effects are observed in those who take mirtazapine recreationally (or one off dosing) most neurophysiological effects are observed in those with on-going use (15, 30 and 45 mg daily prescribed for depression, etc) due to a maintained level of mirtazapine in the body.
-It should be noted that although some of these effects are observed in those who take mirtazapine recreationally (or one off dosing) most neurophysiological effects are observed in those with on-going use (15, 30 and 45mg daily prescribed for depression, etc) due to a maintained level of mirtazapine in the body.
+The oral bioavailability of mirtazapine is about 50%. It is found mostly bound to plasma proteins, about 85%. It is metabolized primarily in the liver by demethylation and hydroxylation via cytochrome P450 enzymes, CYP1A2, CYP2D6, CYP3A4.<ref>Anttila, SA; Leinonen, EV (2001). "A review of the pharmacological and clinical profile of mirtazapine". ''CNS Drug Reviews''. '''7''' (3): 249–64. doi:10.1111/j.1527-3458.2001.tb00198.x. PMC 6494141. <nowiki>PMID 11607047</nowiki>.</ref> One of its major metabolites is desmethylmirtazapine. The overall elimination half-life is 20–40 hours. It is conjugated in the kidney for excretion in the urine, where 75% of the drug is excreted,<ref>Al-Majed, Abdulrahman; Bakheit, Ahmed H.; Alharbi, Raed M.; Abdel Aziz, Hatem A. (1 January 2018). ''Chapter Two - Mirtazapine''. ''Profiles of Drug Substances, Excipients and Related Methodology''. '''43'''. pp. 209–254. doi:10.1016/bs.podrm.2018.01.002. ISBN <bdi>9780128151259</bdi>. <nowiki>PMID 29678261</nowiki>.</ref>  and about 15% is eliminated in feces.<ref>Schatzberg, Alan F. (2009). "Chapter 21: Mirtazapine". In Schatzberg, Alan F.; Nemeroff, Charles B. (eds.). ''The American Psychiatric Publishing Textbook of Psychopharmacology'' (4th ed.). Washington, D.C.: American Psychiatric Pub. ISBN <bdi>9781585623099</bdi>.</ref>
 ==Subjective effects==
@@ Line 117: / Line 122: @@
 ===Combination effects===
 *'''[[Cannabis]]''' - When mirtazapine is combined with cannabis, the euphoric and visual effects are greatly potentiated.
 *'''[[Psychedelics]]''' - Due to mirtazapines action as a 5-HT<sub>2A</sub> antagonist, it can help reduce the intensity or "abort" a [[bad trip]]
@@ Line 124: / Line 130: @@
 {{#ask: [[Category:Mirtazapine]][[Category:Experience]]|format=ul|Columns=1}}
 Additional experience reports can be found here:
-* [https://www.erowid.org/experiences/subs/exp_Pharms_Mirtazapine.shtml Erowid Experience Vaults: Mirtazapine]
+*[https://www.erowid.org/experiences/subs/exp_Pharms_Mirtazapine.shtml Erowid Experience Vaults: Mirtazapine]
 ==Toxicity and harm potential==
@@ Line 144: / Line 151: @@
 ===Dangerous interactions===
 **'''[[UncertainInteraction::Antidepressants]]''' - Different types of antidepressants can cause adverse effects as well as possible [[serotonin syndrome]] when mixed.
@@ Line 155: / Line 163: @@
 ==See also==
 *[[Responsible use]]
 *[[Hallucinogen]]
@@ Line 161: / Line 170: @@
 ==External links==
 *[http://en.wikipedia.org/wiki/Mirtazapine Mirtazapine (Wikipedia)]
 *[http://www.erowid.org/pharms/mirtazapine/mirtazapine.shtml Mirtazapine (Erowid Vault)]
 *[https://isomerdesign.com/PiHKAL/explore.php?domain=pk&id=9430 Mirtazapine (Isomer Design)]
 *[http://www.drugs.com/mirtazapine.html Mirtazapine (Drugs.com)]
 ===Discussion===
 *[http://disregardeverythingisay.com/post/43240860676/mirtazapine-broken-down-and-described Mirtazapine, broken down and described (Disregard Everything I Say)]