Phenelzine

Last updated

Phenelzine
Phenelzine2DACS.svg
Phenelzine3Dan2.gif
Clinical data
Trade names Nardil, others
Other names2-Phenylethylhydrazine; β-Phenylethylhydrazine; Phenethylhydrazine; Phenylethylhydrazine; Phenylethylamine hydrazide; Phenethylamine hydrazide; β-Hydrazinoethylbenzene; Fenelzine; 1-(2-Phenylethyl)hydrazine
AHFS/Drugs.com Monograph
MedlinePlus a682089
License data
Pregnancy
category
Routes of
administration 		By mouth
Drug class Monoamine oxidase inhibitor; Antidepressant
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • BR: Class C1 (Other controlled substances) [2]
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Metabolism Liver
Elimination half-life 11.6 hours
Excretion Urine
Identifiers
  • 2-phenylethylhydrazine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.108 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C8H12N2
Molar mass 136.198 g·mol−1
3D model (JSmol)
Boiling point 74 °C (165 °F)
  • N(N)CCc1ccccc1
  • InChI=1S/C8H12N2/c9-10-7-6-8-4-2-1-3-5-8/h1-5,10H,6-7,9H2 Yes check.svgY
  • Key:RMUCZJUITONUFY-UHFFFAOYSA-N Yes check.svgY
   (verify)

Phenelzine, sold under the brand name Nardil among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine family which is primarily used as an antidepressant and anxiolytic to treat depression and anxiety. [3] Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use. [4]

Contents

Synthesis of phenelzine was first described by Emil Votoček and Otakar Leminger in 1932. [5] [6]

Medical uses

Phenelzine is primarily used in the treatment of major depressive disorder (MDD). Patients with depressive symptomology characterized as "atypical," "nonendogenous," and/or "neurotic" respond particularly well to phenelzine. [7] The medication is also useful in patients who do not respond favorably to first and second-line treatments for depression, or are "treatment-resistant." [8] In addition to being a recognized treatment for major depressive disorder, phenelzine is effective in treating dysthymia, [9] bipolar depression (BD), [10] panic disorder (PD), [11] social anxiety disorder, [12] bulimia nervosa, [13] post-traumatic stress disorder (PTSD), [14] and obsessive–compulsive disorder (OCD). [15] [16]

Side effects

Common side effects of phenelzine may include dizziness, blurry vision, dry mouth, headache, lethargy, sedation, somnolence, insomnia, anorexia, weight gain or loss, small fiber peripheral neuropathy, nausea and vomiting, diarrhea, constipation, urinary retention, mydriasis, muscle tremors, hyperthermia, sweating, hypertension or hypotension, orthostatic hypotension, paresthesia, hepatitis, and sexual dysfunction (consisting of loss of libido and anorgasmia). Rare side effects usually only seen in susceptible individuals may include hypomania or mania, psychosis and acute liver failure, the last of which is usually only seen in people with pre-existing liver damage, old age, long-term effects of alcohol consumption, or viral infection. [17]

Interactions

The MAOIs have certain dietary restrictions and drug interactions. A hypertensive crisis may result from the overconsumption of tyramine-containing foods, although it is a rare occurrence. [18] [19] Serotonin syndrome may result from an interaction with certain drugs which increase serotonin activity such as selective serotonin reuptake inhibitors, serotonin releasing agents, and serotonin agonists. [20] [21]

Phenelzine has also been linked to vitamin B6 deficiency. [22] Transaminases such as GABA-transaminase have been shown to be dependent upon vitamin B6 [23] and may be involved in a potentially related process, since the phenelzine metabolite phenylethylidenehydrazine (PEH) is a GABA-transaminase inhibitor. Both phenelzine and vitamin B6 are rendered inactive upon these reactions occurring. The pyridoxine form of B6 is recommended for supplementation, since this form has been shown to reduce hydrazine toxicity from phenelzine and, in contrast, the pyridoxal form has been shown to increase the toxicity of hydrazines. [24]

Pharmacology

Pharmacodynamics

Phenelzine is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It inhibits both of the respective isoforms of MAO, MAO-A and MAO-B, and does so almost equally, with a slight preference for the former. By inhibiting MAO, phenelzine prevents the breakdown of the monoamine neurotransmitters serotonin, melatonin, norepinephrine, epinephrine, and dopamine, as well as the trace amine neuromodulators such as phenethylamine, tyramine, octopamine, and tryptamine. This leads to an increase in the extracellular concentrations of these neurochemicals and, therefore, an alteration in neurochemistry and neurotransmission. This action is thought to be the primary mediator in phenelzine's therapeutic benefits. [25]

Phenelzine and its metabolites also inhibit at least two other enzymes to a lesser extent, of which are alanine transaminase (ALA-T), [26] and γ-aminobutyric acid transaminase (GABA-T), [27] the latter of which is not caused by phenelzine itself, but by a phenelzine metabolite phenylethylidenehydrazine (PEH). By inhibiting ALA-T and GABA-T, phenelzine causes an increase in the alanine and GABA levels in the brain and body. [28] GABA is the major inhibitory neurotransmitter in the mammalian central nervous system, and is very important for the normal suppression of anxiety, stress, and depression. Phenelzine's action in increasing GABA concentrations may significantly contribute to its antidepressant, and especially, anxiolytic/antipanic properties, the latter of which have been considered superior to those of other antidepressants. As for ALA-T inhibition, though the consequences of disabling this enzyme are currently not well understood, there is some evidence to suggest that it is this action of the hydrazines (including phenelzine) which may be responsible for the occasional incidence of hepatitis and liver failure. [29]

Phenelzine has also been shown to metabolize to phenethylamine (PEA). [30] PEA acts as a releasing agent of norepinephrine and dopamine, which occurs in a similar manner to amphetamine by being taken up into vesicles, displacing and causing the release of those monoamines, and reversing monoamine flux through their respective transporters via TAAR1 agonism (though with markedly shorter pharmacokinetics). [31]

Like many other antidepressants, phenelzine usually requires several weeks of treatment to achieve full therapeutic effects. The reason for this delay is not fully understood. Still, it is believed to be due to many factors, including achieving steady-state levels of MAO inhibition and the resulting adaptations in mean neurotransmitter levels, the possibility of necessary desensitization of autoreceptors which generally inhibit the release of neurotransmitters like serotonin and dopamine, and also the upregulation of enzymes such as serotonin N-acetyltransferase. Typically, a therapeutic response to MAOIs is associated with an inhibition of at least 80-85% of monoamine oxidase activity. [32]

Pharmacokinetics

Phenelzine 15 mg tablets. NardilTablets.jpg
Phenelzine 15 mg tablets.

Phenelzine is administered orally in the form of phenelzine sulfate [4] and is rapidly absorbed from the gastrointestinal tract. [33] The time to peak plasma concentration is 43 minutes, and the half-life is 11.6 hours. [34] Unlike most other drugs, phenelzine irreversibly disables MAO. As a result, it does not necessarily need to be present in the blood at all times for its effects to be sustained. Because of this, upon phenelzine treatment being ceased, its effects typically do not wear off until the body replenishes its enzyme stores, a process which can take as long as 2–3 weeks. [4]

Phenelzine is metabolized primarily in the liver, and its metabolites are excreted in the urine. Oxidation is the primary routine of metabolism, and the major metabolites are phenylacetic acid and parahydroxyphenylacetic acid, recovered as about 73% of the excreted dose of phenelzine in the urine over 96 hours after single doses. Acetylation to N2-acetylphenelzine is a minor pathway. [35] [36] Phenelzine may also interact with cytochrome P450 enzymes, inactivating these enzymes through the formation of a heme adduct. [37] Two other minor metabolites of phenelzine, as mentioned above, include phenylethylidenehydrazine and phenethylamine. [38]

Chemistry

Phenelzine, also known as 2-phenylethylhydrazine or phenylethylamine hydrazide, is a phenethylamine and hydrazine derivative. [39] [40] It is the hydrazide of β-phenethylamine and can also be referred to as N-aminophenethylamine. [39] [40]

Close analogues of phenelzine include the amphetamine and hydrazine derivatives pheniprazine (α-methylphenelzine; the corresponding amphetamine analogue) and metfendrazine (α,N-dimethylphenelzine; the corresponding methamphetamine analogue), among others. [41] [42]

Research

Phenelzine showed promise in a phase II clinical trial from March 2020 in treating prostate cancer. [43] Phenelzine has also been shown to have neuroprotective effects in animal models. [44] [45] [46]

Related Research Articles

<span class="mw-page-title-main">Antidepressant</span> Class of medication used to treat depression and other conditions

Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.

An anxiolytic is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiety disorders and their related psychological and physical symptoms.

<span class="mw-page-title-main">Monoamine oxidase inhibitor</span> Type of medication

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, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.

<span class="mw-page-title-main">Monoamine oxidase</span> Family of enzymes

Monoamine oxidases (MAO) are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first such enzyme was discovered in 1928 by Mary Bernheim in the liver and was named tyramine oxidase. The MAOs belong to the protein family of flavin-containing amine oxidoreductases.

<span class="mw-page-title-main">Serotonin syndrome</span> Symptoms caused by an excess of serotonin in the central nervous system

Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild cases include high blood pressure and a fast heart rate; usually without a fever. Symptoms in moderate cases include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. In severe cases, body temperature can increase to greater than 41.1 °C (106.0 °F). Complications may include seizures and extensive muscle breakdown.

A psychiatric or psychotropic medication is a psychoactive drug taken to exert an effect on the chemical makeup of the brain and nervous system. Thus, these medications are used to treat mental illnesses. These medications are typically made of synthetic chemical compounds and are usually prescribed in psychiatric settings, potentially involuntarily during commitment. Since the mid-20th century, such medications have been leading treatments for a broad range of mental disorders and have decreased the need for long-term hospitalization, thereby lowering the cost of mental health care. The recidivism or rehospitalization of the mentally ill is at a high rate in many countries, and the reasons for the relapses are under research.

<span class="mw-page-title-main">Phenethylamine</span> Organic compound, a stimulant in humans

Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. To a lesser extent, it also acts as a neurotransmitter in the human central nervous system. In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.

<span class="mw-page-title-main">Tranylcypromine</span> Irreversible non-selective MAO inhibitor Antidepressant drug

Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively. It is also effective in the treatment of ADHD.

<span class="mw-page-title-main">Serotonin–norepinephrine reuptake inhibitor</span> Class of antidepressant medication

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. Off-label uses include treatments for attention-deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and migraine prevention. SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which act upon single neurotransmitters.

<span class="mw-page-title-main">Selegiline</span> Monoamine oxidase inhibitor

Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl, Zelapar, and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It has also been studied and used off-label for a variety of other indications, but has not been formally approved for any other use. The medication, in the form licensed for depression, has modest effectiveness for this condition that is similar to that of other antidepressants. Selegiline is provided as a swallowed tablet or capsule or an orally disintegrating tablet (ODT) for Parkinson's disease and as a patch applied to skin for depression.

<span class="mw-page-title-main">Isocarboxazid</span> Antidepressant

Isocarboxazid is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class used as an antidepressant. Along with phenelzine and tranylcypromine, it is one of only three classical MAOIs still available for clinical use in the treatment of psychiatric disorders in the United States, though it is not as commonly employed in comparison to the others.

<span class="mw-page-title-main">Moclobemide</span> Antidepressant

Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety. It is not approved for use in the United States, but is approved in other Western countries such as Canada, the UK and Australia. It is produced by affiliates of the Hoffmann–La Roche pharmaceutical company. Initially, Aurorix was also marketed by Roche in South Africa, but was withdrawn after its patent rights expired and Cipla Medpro's Depnil and Pharma Dynamic's Clorix became available at half the cost.

<span class="mw-page-title-main">Iproniazid</span> Antidepressant

Iproniazid is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class. It is a xenobiotic that was originally designed to treat tuberculosis, but was later most prominently used as an antidepressant drug. However, it was withdrawn from the market because of its hepatotoxicity. The medical use of iproniazid was discontinued in most of the world in the 1960s, but remained in use in France until its discontinuation in 2015.

<span class="mw-page-title-main">Rasagiline</span> Chemical compound

Rasagiline, sold under the brand name Azilect among others, is a medication which is used in the treatment of Parkinson's disease. It is used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases. The drug is taken by mouth.

<span class="mw-page-title-main">Pargyline</span> Chemical compound

Pargyline, sold under the brand name Eutonyl among others, is a monoamine oxidase inhibitor (MAOI) medication which has been used to treat hypertension but is no longer marketed. It has also been studied as an antidepressant, but was never licensed for use in the treatment of depression. The drug is taken by mouth.

A serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), also known as a triple reuptake inhibitor (TRI), is a type of drug that acts as a combined reuptake inhibitor of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine. It does this by concomitantly inhibiting the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), respectively. Inhibition of the reuptake of these neurotransmitters increases their extracellular concentrations and, therefore, results in an increase in serotonergic, adrenergic, and dopaminergic neurotransmission. The naturally-occurring and potent SNDRI cocaine is widely used recreationally and often illegally for the euphoric effects it produces.

<span class="mw-page-title-main">Monoamine oxidase B</span> Protein-coding gene in the species Homo sapiens

Monoamine oxidase B (MAO-B) is an enzyme that in humans is encoded by the MAOB gene.

<span class="mw-page-title-main">Pheniprazine</span> Chemical compound

Pheniprazine, formerly sold under the brand names Catron and Cavodil, is an irreversible and non-selective monoamine oxidase inhibitor (MAOI) of the hydrazine group that was used as an antidepressant to treat depression in the 1960s. It was also used in the treatment of angina pectoris and schizophrenia. Pheniprazine has been largely discontinued due to toxicity concerns such as jaundice, amblyopia, and optic neuritis.

<span class="mw-page-title-main">Metfendrazine</span> Chemical compound

Metfendrazine, also known as methphendrazine, is an irreversible and nonselective monoamine oxidase inhibitor (MAOI) of the hydrazine family. It was investigated as an antidepressant, but was never marketed.

<span class="mw-page-title-main">Hydrazine (antidepressant)</span> Group of antidepressants

The hydrazine antidepressants are a group of non-selective, irreversible monoamine oxidase inhibitors (MAOIs) which were discovered and initially marketed in the 1950s and 1960s. Most have been withdrawn due to toxicity, namely hepatotoxicity, but a few still remain in clinical use.

References

  1. ↑ "Phenelzine (Nardil) Use During Pregnancy". Drugs.com. 3 March 2020. Retrieved 11 July 2020.
  2. ↑ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  3. ↑ "Phenelzine". MedlinePlus Drug Information. U.S. National Library of Medicine. Retrieved 27 October 2023.
  4. 1 2 3 Sidhu G, Marwaha R (2023). "Phenelzine". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   32119395 . Retrieved 23 November 2023.
  5. ↑ Budavari S, O'Neil, Smith A, Heckelman PE, Kinneary JF (1996). "Phenelzine". The Merck Index (12th ed.). Whitehouse Station: Merck & Co. 7181.
  6. ↑ Votoček E, Leminger O (1932). "Sur la β-phenoéthylhydrazine" [On the [preparation and properties of] β-phenoethylhydrazine]. Collection of Czechoslovak Chemical Communications (in French). 4: 271–281. doi:10.1135/cccc19320271.
  7. ↑ Parke-Davis Division of Pfizer Inc. (2007). "Nardil(R) (Phenelzine sulfate tablets, USP), labeling information" (PDF). U.S. Food and Drug Administration's. Archived (PDF) from the original on 27 November 2009. Retrieved 14 December 2009.
  8. ↑ Fiedorowicz JG, Swartz KL (July 2004). "The role of monoamine oxidase inhibitors in current psychiatric practice". Journal of Psychiatric Practice. 10 (4): 239–248. doi:10.1097/00131746-200407000-00005. PMC   2075358 . PMID   15552546.
  9. ↑ Vallejo J, Gasto C, Catalan R, Salamero M (November 1987). "Double-blind study of imipramine versus phenelzine in Melancholias and Dysthymic Disorders". The British Journal of Psychiatry. 151 (5): 639–642. doi:10.1192/bjp.151.5.639. PMID   3446308. S2CID   145651628.
  10. ↑ Quitkin FM, McGrath P, Liebowitz MR, Stewart J, Howard A (March 1981). "Monoamine oxidase inhibitors in bipolar endogenous depressives". Journal of Clinical Psychopharmacology. 1 (2): 70–74. doi:10.1097/00004714-198103000-00005. PMID   7028797. S2CID   32909169.
  11. ↑ Buigues J, Vallejo J (February 1987). "Therapeutic response to phenelzine in patients with panic disorder and agoraphobia with panic attacks". The Journal of Clinical Psychiatry. 48 (2): 55–59. PMID   3542985.
  12. ↑ Blanco C, Schneier FR, Schmidt A, Blanco-Jerez CR, Marshall RD, Sánchez-Lacay A, et al. (2003). "Pharmacological treatment of social anxiety disorder: a meta-analysis". Depression and Anxiety. 18 (1): 29–40. doi:10.1002/da.10096. PMID   12900950. S2CID   12296484.
  13. ↑ Walsh BT, Gladis M, Roose SP, Stewart JW, Stetner F, Glassman AH (May 1988). "Phenelzine vs placebo in 50 patients with bulimia". Archives of General Psychiatry. 45 (5): 471–475. doi:10.1001/archpsyc.1988.01800290091011. PMID   3282482.
  14. ↑ Frank JB, Kosten TR, Giller EL, Dan E (October 1988). "A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder". The American Journal of Psychiatry. 145 (10): 1289–1291. doi:10.1176/ajp.145.10.1289. PMID   3048121.
  15. ↑ Vallejo J, Olivares J, Marcos T, Bulbena A, Menchón JM (November 1992). "Clomipramine versus phenelzine in obsessive-compulsive disorder. A controlled clinical trial". The British Journal of Psychiatry. 161 (5): 665–670. doi:10.1192/bjp.161.5.665. PMID   1422616. S2CID   36232956.
  16. ↑ Grant JE, Baldwin DS, Chamberlain SR (July 2021). "Time to Reconsider Monoamine Oxidase Inhibitors for Obsessive Compulsive Disorder?: A Case Series Using Phenelzine". Journal of Clinical Psychopharmacology. 41 (4): 461–464. doi:10.1097/JCP.0000000000001418. PMID   34108430. S2CID   235395484.
  17. ↑ Gómez-Gil E, Salmerón JM, Mas A (April 1996). "Phenelzine-induced fulminant hepatic failure". Annals of Internal Medicine. 124 (7): 692–693. doi:10.7326/0003-4819-124-7-199604010-00014. PMID   8607601. S2CID   43020372.
  18. ↑ Gillman PK (January 2019). "The risk of harm from acute tyramine-induced hypertension: how significant?". PsychoTropical Commentaries. 5: 1–10. doi:10.13140/RG.2.2.11909.40165. Archived from the original on 8 January 2022. Retrieved 8 January 2022.[ self-published source? ]
  19. ↑ Grady MM, Stahl SM (March 2012). "Practical guide for prescribing MAOIs: debunking myths and removing barriers". CNS Spectrums. 17 (1): 2–10. doi:10.1017/S109285291200003X. PMID   22790112. S2CID   206312008.
  20. ↑ Scotton WJ, Hill LJ, Williams AC, Barnes NM (2019). "Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions". International Journal of Tryptophan Research. 12: 1178646919873925. doi:10.1177/1178646919873925. PMC   6734608 . PMID   31523132.
  21. ↑ Volpi-Abadie J, Kaye AM, Kaye AD (2013). "Serotonin syndrome". Ochsner Journal. 13 (4): 533–540. PMC   3865832 . PMID   24358002.
  22. ↑ Malcolm DE, Yu PH, Bowen RC, O'Donovan C, Hawkes J, Hussein M (November 1994). "Phenelzine reduces plasma vitamin B6". Journal of Psychiatry & Neuroscience. 19 (5): 332–334. PMC   1188621 . PMID   7803366.
  23. ↑ PDB: 1OHW ​; Storici P, De Biase D, Bossa F, Bruno S, Mozzarelli A, Peneff C, et al. (January 2004). "Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin". The Journal of Biological Chemistry. 279 (1): 363–373. doi: 10.1074/jbc.M305884200 . PMID   14534310.
  24. ↑ Dubnick B, Leeson GA, Scott CC (July 1960). "Effect of forms of vitamin B6 on acute toxicity of hydrazines". Toxicology and Applied Pharmacology. 2 (4): 403–409. doi:10.1016/0041-008X(60)90007-7. PMID   13818307.
  25. ↑ Baker GB, Coutts RT, McKenna KF, Sherry-McKenna RL (November 1992). "Insights into the mechanisms of action of the MAO inhibitors phenelzine and tranylcypromine: a review". Journal of Psychiatry & Neuroscience. 17 (5): 206–214. PMC   1188458 . PMID   1362653.
  26. ↑ Tanay VA, Parent MB, Wong JT, Paslawski T, Martin IL, Baker GB (August 2001). "Effects of the antidepressant/antipanic drug phenelzine on alanine and alanine transaminase in rat brain". Cellular and Molecular Neurobiology. 21 (4): 325–339. doi:10.1023/A:1012697904299. PMID   11775064. S2CID   20655821.
  27. ↑ McKenna KF, McManus DJ, Baker GB, Coutts RT (1994). "Chronic administration of the antidepressant phenelzine and its N-acetyl analogue: Effects on GABAergic function". In Tipton KF, Youdim MB, Barwell CJ, Callingham BA, Lyles GA (eds.). Amine Oxidases: Function and Dysfunction. Journal of Neural Transmission. Supplementum. Vol. 41. pp. 115–122. doi:10.1007/978-3-7091-9324-2_15. ISBN   978-3-211-82521-1. PMID   7931216.
  28. ↑ Paslawski TM (1998). The Antipanic Drug Phenelzine and Its Effects on GABA and Related Amino Acids (Ph.D. thesis). University of Alberta. ISBN   978-0-612-29091-4. OCLC   46576166.
  29. ↑ Gómez-Gil E, Salmerón JM, Mas A (April 1996). "Phenelzine-induced fulminant hepatic failure". Annals of Internal Medicine. 124 (7): 692–693. doi:10.7326/0003-4819-124-7-199604010-00014. PMID   8607601.
  30. ↑ Dyck LE, Durden DA, Boulton AA (June 1985). "Formation of beta-phenylethylamine from the antidepressant, beta-phenylethylhydrazine". Biochemical Pharmacology. 34 (11): 1925–1929. doi:10.1016/0006-2952(85)90310-7. PMID   4004908.
  31. ↑ Heal DJ, Smith SL, Gosden J, Nutt DJ (June 2013). "Amphetamine, past and present--a pharmacological and clinical perspective". Journal of Psychopharmacology. 27 (6): 479–496. doi:10.1177/0269881113482532. PMC   3666194 . PMID   23539642.
  32. ↑ Raft D, Davidson J, Wasik J, Mattox A (1981). "Relationship between response to phenelzine and MAO inhibition in a clinical trial of phenelzine, amitriptyline and placebo". Neuropsychobiology. 7 (3): 122–126. doi:10.1159/000117841. PMID   7231652.
  33. ↑ "Phenelzine". go.drugbank.com. Retrieved 23 November 2023.
  34. ↑ "Phenelzine: Package Insert". Drugs.com. Retrieved 23 November 2023.
  35. ↑ "NARDIL- phenelzine sulfate tablet, film coated" (PDF). DailyMed . Archived (PDF) from the original on 20 May 2024. Retrieved 20 May 2024.
  36. ↑ Kallem RR, Jillela B, Ravula AR, Samala R, Andy A, Ramesh M, et al. (June 2016). "Highly sensitive LC-MS/MS-ESI method for determination of phenelzine in human plasma and its application to a human pharmacokinetic study". Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 1022: 126–132. doi:10.1016/j.jchromb.2016.04.006. PMID   27085800.
  37. ↑ Polasek TM, Elliot DJ, Somogyi AA, Gillam EM, Lewis BC, Miners JO (May 2006). "An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid". British Journal of Clinical Pharmacology. 61 (5): 570–584. doi:10.1111/j.1365-2125.2006.02627.x. PMC   1885050 . PMID   16669850.
  38. ↑ Matveychuk D, MacKenzie EM, Kumpula D, Song MS, Holt A, Kar S, et al. (January 2022). "Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine". Cellular and Molecular Neurobiology. 42 (1): 225–242. doi:10.1007/s10571-021-01078-3. PMC   8732914 . PMID   33839994.
  39. 1 2 Shulgin A, Manning T, Daley DF (2011). The Shulgin Index: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Transform Press. ISBN   978-0-9630096-3-0 . Retrieved 12 August 2024. [...] phenelzine (N-amino-phenethylamine, an anxiolytic) [...]
  40. 1 2 "PiHKAL·info". Isomer Design. 4 August 2024. Retrieved 12 August 2024.
  41. ↑ Secci D, Bolasco A, Chimenti P, Carradori S (2011). "The state of the art of pyrazole derivatives as monoamine oxidase inhibitors and antidepressant/anticonvulsant agents". Curr Med Chem. 18 (33): 5114–5144. doi:10.2174/092986711797636090. PMID   22050759.
  42. ↑ Yáñez M, Padín JF, Arranz-Tagarro JA, Camiña M, Laguna R (2012). "History and therapeutic use of MAO-A inhibitors: a historical perspective of MAO-A inhibitors as antidepressant drug". Curr Top Med Chem. 12 (20): 2275–2282. doi:10.2174/156802612805220011. PMID   23231399.
  43. ↑ Stone L (April 2020). "MAOA inhibitor phenelzine efficacious in recurrent prostate cancer". Nature Reviews. Urology. 17 (4): 192. doi: 10.1038/s41585-020-0307-y . PMID   32203303. S2CID   212681980.
  44. ↑ Baker G, Matveychuk D, MacKenzie EM, Holt A, Wang Y, Kar S (May 2019). "Attenuation of the effects of oxidative stress by the MAO-inhibiting antidepressant and carbonyl scavenger phenelzine". Chemico-Biological Interactions. 304: 139–147. Bibcode:2019CBI...304..139B. doi: 10.1016/j.cbi.2019.03.003 . PMID   30857888. S2CID   75140657.
  45. ↑ Matveychuk D, MacKenzie EM, Kumpula D, Song MS, Holt A, Kar S, et al. (January 2022). "Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine". Cellular and Molecular Neurobiology. 42 (1): 225–242. doi: 10.1007/s10571-021-01078-3 . PMC   8732914 . PMID   33839994. S2CID   233211407.
  46. ↑ Cebak JE, Singh IN, Hill RL, Wang JA, Hall ED (April 2017). "Phenelzine Protects Brain Mitochondrial Function In Vitro and In Vivo following Traumatic Brain Injury by Scavenging the Reactive Carbonyls 4-Hydroxynonenal and Acrolein Leading to Cortical Histological Neuroprotection". Journal of Neurotrauma. 34 (7): 1302–1317. doi:10.1089/neu.2016.4624. PMC   5385448 . PMID   27750484.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.