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Phenelzine

From Wikipedia, the free encyclopedia
(Redirected from Nardil)

Phenelzine
Molecular structure of phenelzine
3D representation of a phenelzine molecule
Clinical data
Trade namesNardil, others
Other names2-Phenylethylhydrazine; β-Phenylethylhydrazine; Phenethylhydrazine; Phenylethylhydrazine; Phenylethylamine hydrazide; Phenethylamine hydrazide; β-Hydrazinoethylbenzene; Fenelzine; 1-(2-Phenylethyl)hydrazine
AHFS/Drugs.comMonograph
MedlinePlusa682089
License data
Pregnancy
category
Routes of
administration		By mouth
Drug classMonoamine 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
MetabolismLiver
Elimination half-life11.6 hours
ExcretionUrine
Identifiers
  • 2-phenylethylhydrazine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.108 Edit this at Wikidata
Chemical and physical data
FormulaC8H12N2
Molar mass136.198 g·mol−1
3D model (JSmol)
Boiling point74 °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 checkY
  • Key:RMUCZJUITONUFY-UHFFFAOYSA-N checkY
  (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][4] Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use.[3][5]

Medical uses

[edit]

Phenelzine is primarily used in the treatment of major depressive disorder, including treatment-resistant depression. Modern guidance on classic MAOIs recommends considering phenelzine, tranylcypromine, or isocarboxazid after insufficient response to other antidepressant treatments and before electroconvulsive therapy when a rapid treatment response is not required.[6]

Patients with atypical depression may respond particularly well to phenelzine,[7] but evidence also supports the use of classic MAOIs in melancholic depression.[8] Phenelzine may be especially useful when depression is accompanied by premorbid anxiety, comorbid panic disorder, or other treatment-resistant anxiety symptoms, reflecting its additional effects on GABA metabolism.[6]

Phenelzine has also been studied or used in anxiety-related and other psychiatric conditions including panic disorder,[9] social anxiety disorder,[10] post-traumatic stress disorder (PTSD),[11] obsessive–compulsive disorder (OCD),[12][13] dysthymia,[14] bipolar depression,[15] and bulimia nervosa.[16]

Side effects

[edit]

Common or clinically important adverse effects of phenelzine include orthostatic hypotension, dizziness, dry mouth, constipation, urinary retention, sedation or somnolence, insomnia, weight gain, edema, sweating, sexual dysfunction, and reduced vitamin B6 levels or pyridoxine deficiency. Hypoglycemia and clinically relevant cytochrome P450 interactions may also occur, particularly with hydrazine MAOIs such as phenelzine.[6]

Rare adverse effects reported with phenelzine include hypomania or mania, psychosis, hepatotoxicity, and acute liver failure, the last of which has been reported mainly in susceptible individuals, including people with pre-existing liver damage, old age, long-term effects of alcohol consumption, or viral infection.[17]

Contraindications

[edit]

Phenelzine is contraindicated in patients who are unable or unwilling to follow the required dietary tyramine restrictions and medication precautions, and in patients with pheochromocytoma because of the risk of hypertensive emergency. This contraindication reflects a preventable risk: tyramine-related hypertensive emergencies are uncommon when dietary and medication precautions are followed, and modern food standards have substantially reduced excessive tyramine exposure compared with the period when MAOIs were first introduced.[6] It is also contraindicated with drugs, supplements, or recreational drugs that have significant serotonin reuptake inhibition or significant serotonin-releasing activity, because of the risk of serotonin toxicity. Examples include selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), clomipramine, imipramine, MDMA, and certain analgesics such as meperidine, tramadol, methadone, tapentadol, dextromethorphan, dextropropoxyphene, pentazocine, and levorphanol.[6]

Concomitant use of multiple MAO-inhibiting agents is generally listed as contraindicated or avoided in prescribing guidance. For combinations of classic MAOIs with one another, the caution is based mainly on limited safety data and the fact that routine long-term coadministration usually has little therapeutic rationale, since classic MAOIs already inhibit both MAO-A and MAO-B irreversibly. This concern is not the same as the serotonin-toxicity risk seen when MAOIs are combined with drugs that significantly inhibit serotonin reuptake or release serotonin. A classic MAOI-to-classic MAOI overlap is not expected to cause serotonin toxicity unless another serotonergic drug with clinically significant serotonin reuptake inhibition or serotonin-releasing activity is also involved.[6]

This should be distinguished from medically supervised switching between classic MAOIs, where shorter washouts, direct switches, or cautious cross-tapering have been used by some expert clinicians under close monitoring. In that context, temporary MAOI-to-MAOI overlap may have practical utility, such as reducing relapse risk or avoiding a prolonged untreated interval when changing from one MAOI to another because of adverse effects or inadequate response.[6][18]

Drugs described as "stimulants" are not a uniform pharmacological category and are not uniformly contraindicated with phenelzine. Modern MAOI guidance distinguishes amphetamines by dose: medium or high doses are avoided because of serotonin-releasing activity, while low-dose amphetamines are listed as a strong relative contraindication rather than an absolute contraindication. When used by experienced clinicians, they require specialist caution, reduced starting doses, slow titration, and blood-pressure monitoring. Lisdexamfetamine may be lower risk than some other amphetamine preparations because of its lower peak plasma concentration and longer time to peak concentration.[6]

Ephedrine and pseudoephedrine are also relative, not absolute, contraindications. They are generally avoided or used only cautiously at reduced doses with monitoring because they may raise blood pressure. Pseudoephedrine is less potent than ephedrine, and ephedrine is less potent than amphetamine.[6]

Phenelzine generally does not need to be stopped before surgery solely because anesthesia is planned. Modern guidance states that MAOI treatment should not be discontinued without conferring with the prescribing psychiatrist, because depressive relapse risk may outweigh perioperative interaction risk when anesthetic and analgesic agents are chosen carefully.[6] In perioperative care, the main drugs to avoid are those with significant serotonin reuptake inhibition or serotonin-releasing activity, especially serotonergic opioid analgesics such as meperidine (pethidine) and tramadol. Other opioids listed as serotonergic or uncertain-risk include methadone, tapentadol, dextromethorphan, dextropropoxyphene, pentazocine, and levorphanol.[6]

Other perioperative agents requiring avoidance or special caution include pancuronium, a muscle relaxant sometimes used with general anesthetics, and methylene blue, which has clinically relevant MAOI activity itself. These are not avoided because they are serotonin reuptake inhibitors. Direct-acting vasopressors such as epinephrine, norepinephrine, and phenylephrine are not absolute contraindications, but lower initial doses and careful titration are advised because their pressor effects may be potentiated. Indirect sympathomimetics such as ephedrine are generally avoided or used only cautiously because they may raise blood pressure.[6]

Methylphenidate should be distinguished from amphetamines because it is primarily a dopamine reuptake inhibitor rather than a monoamine releaser. Modern guidance lists methylphenidate, modafinil, and bupropion among augmenting agents that can be combined with MAOIs using a low test dose, slow dose increases, and monitoring.[6] A review of stimulant–MAOI combinations found no documented reports of hypertensive crises or fatalities when stimulants were cautiously added to an MAOI.[19]

Other relative contraindications or situations requiring special caution include uncontrolled hypertension or hypotension, diabetes mellitus, pregnancy, breastfeeding, bipolar disorder without mood-stabilizing treatment, and lack of recent health assessment.[6]

Interactions

[edit]

Phenelzine requires attention to dietary tyramine and clinically important drug interactions, but severe tyramine-related hypertensive reactions are uncommon when dietary and medication precautions are followed. Modern food standards have substantially reduced tyramine levels in many foods compared with the 1950s and 1960s, making excessive tyramine ingestion less likely than in earlier decades. The highest-risk foods are generally those that are fermented, matured, or spoiled, including some aged cheeses, some artisan beers, fermented meats, and fermented products such as soy sauce, miso, tempeh, sauerkraut, Marmite, and kimchi.[6]

Because inhibition of monoamine oxidase reduces the breakdown of dietary tyramine in the gastrointestinal tract and liver, excessive tyramine intake can raise blood pressure through peripheral norepinephrine release. If this causes a marked blood-pressure rise, the reaction is usually self-limiting and typically reaches its maximum within about 2 hours. Modern guidance advises against rapid blood-pressure reduction outside appropriate medical supervision, because overtreatment can cause hypotensive overshoot; sublingual nifedipine is specifically discouraged. The Cambridge Prescriber's Guide recommends benzodiazepine administration with blood-pressure monitoring, with emergency clinicians using clinical judgment in severe cases and considering short-acting agents such as phentolamine when additional treatment is needed.[6] A safety review reported that deaths from tyramine/MAOI-induced hypertension are extremely rare and that no deaths from MAOI-induced hypertension had been reported in the medical literature for several decades.[20]

Phenelzine should not be combined with drugs that have significant serotonin reuptake inhibition or significant serotonin-releasing activity, because of the risk of serotonin toxicity. Examples include selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), clomipramine, imipramine, MDMA, and certain analgesics such as meperidine, tramadol, methadone, tapentadol, dextromethorphan, dextropropoxyphene, pentazocine, and levorphanol. This serotonin-toxicity mechanism is distinct from the usual caution about overlapping MAO-inhibiting agents. Classic MAOI-to-classic MAOI overlap is not expected to cause serotonin toxicity by itself, although routine long-term coadministration is generally avoided because of limited safety data and lack of usual therapeutic rationale.[6]

Indirect monoamine-releasing sympathomimetics without significant serotonergic activity, such as ephedrine and pseudoephedrine, are not absolute contraindications, but may increase blood pressure and are generally avoided or used only cautiously at reduced doses with monitoring. Pseudoephedrine is considered less potent than ephedrine, and ephedrine less potent than amphetamine.[6]

Direct adrenergic agents such as epinephrine, norepinephrine, phenylephrine, isoproterenol, and dobutamine may be used when clinically necessary, but reduced initial doses and careful monitoring are advised because of possible potentiation.[6]

Phenelzine has also been linked to reduced vitamin B6 levels and pyridoxine deficiency.[21] Modern guidance considers pyridoxine hydrochloride supplementation advisable with phenelzine, either from the start of treatment or if related adverse effects appear, according to clinician preference, and specifically recommends it when paresthesia or peripheral neuropathy occurs.[6] Transaminases such as GABA-transaminase have been shown to be dependent upon vitamin B6[22] 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 generally preferred for supplementation in this context, 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.[23]

Pharmacology

[edit]

Pharmacodynamics

[edit]

Phenelzine is a non-selective and irreversible inhibitor of monoamine oxidase. It inhibits both MAO-A and MAO-B, with only slight preference for MAO-A. By inhibiting monoamine oxidase, phenelzine reduces the metabolic breakdown of serotonin, norepinephrine, dopamine, and related trace amines. Classic MAOIs increase the absolute amount of these neurotransmitters within as well as outside neurons, unlike reuptake inhibitors, which mainly produce relative extracellular increases by blocking transporter-mediated reuptake. This mechanism, together with phenelzine's additional effects on GABA metabolism, is thought to contribute to its antidepressant and anxiolytic effects.[6]

Phenelzine and its metabolites also inhibit other enzymes to a lesser extent, two of which are alanine transaminase (ALA-T),[24] and γ-aminobutyric acid transaminase (GABA-T),[25] the latter of which is not caused by phenelzine itself, but by phenylethylidenehydrazine (PEH), which is a phenelzine metabolite. By inhibiting GABA-T and ALA-T, phenelzine causes an increase in the alanine and GABA levels in the brain and body.[26] GABA is the major inhibitory neurotransmitter in the central nervous system of mammals, 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.[27]

Phenelzine has also been shown to metabolize to phenethylamine (PEA).[28] 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 (though with markedly shorter pharmacokinetics).[29]

Phenelzine usually requires several weeks of treatment to achieve full therapeutic effects. Modern guidance notes that while some improvement may occur within days or weeks, the full antidepressant effect of a given dose may take 4 to 6 weeks, and with phenelzine may take 8 to 12 weeks. A therapeutic response to MAOIs has historically been associated with inhibition of at least 80–85% of monoamine oxidase activity.[6][30]

Pharmacokinetics

[edit]
Phenelzine 15 mg tablets.

Phenelzine is administered orally in the form of phenelzine sulfate[5] and is rapidly absorbed from the gastrointestinal tract.[31] The time to peak plasma concentration is 43 minutes, and the half-life is 11.6 hours.[32] Since phenelzine irreversibly disables MAO, 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.[5]

Phenelzine is metabolized primarily in the liver, and its metabolites are excreted in the urine. Oxidation is the primary route 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.[33][34] Phenelzine may also interact with cytochrome P450 enzymes, inactivating these enzymes through the formation of a heme adduct.[35] Two other minor metabolites of phenelzine, as mentioned above, include phenylethylidenehydrazine and phenethylamine.[36]

Chemistry

[edit]
Phenelzine hydrochloride powder.

Phenelzine, also known as 2-phenylethylhydrazine or phenylethylamine hydrazide, is a phenethylamine and hydrazine derivative.[37][38] It is the hydrazide of β-phenethylamine and can also be referred to as N-aminophenethylamine.[37][38]

Synthesis

[edit]

The chemical synthesis of phenelzine has been described.[3]

Analogues

[edit]

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.[39][40] Other analogues of phenelzine are its deuterated isotopologues α,α-dideuterophenelzine (d2-phenelzine) and α,α,β,β-tetradeuterophenelzine (d4-phenelzine), which show strongly potentiated pharmacological activity compared to phenelzine.[41][42][43][44][45][46]

History

[edit]

Synthesis of phenelzine was first described by Emil Votoček and Otakar Leminger in 1932.[47][48]

Research

[edit]

Phenelzine showed promise in a phase II clinical trial from March 2020 in treating prostate cancer.[49] Phenelzine has also been shown to have neuroprotective effects in animal models.[50][51][52]

References

[edit]
  1. ↑ "Phenelzine (Nardil) Use During Pregnancy". Drugs.com. 3 March 2020. Retrieved 2020-07-11.
  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 2023-08-03. Retrieved 2023-08-16.
  3. 1 2 3 Hoffman GR, Olson MG, Schoffstall AM, Estévez RF, Van den Eynde V, Gillman PK, et al. (December 2023). "Classics in Chemical Neuroscience: Selegiline, Isocarboxazid, Phenelzine, and Tranylcypromine". ACS Chem Neurosci. 14 (23): 4064–4075. doi:10.1021/acschemneuro.3c00591. PMID 37966854.
  4. ↑ "Phenelzine". MedlinePlus Drug Information. U.S. National Library of Medicine. Retrieved 2023-10-27.
  5. 1 2 3 Sidhu G, Marwaha R (2023). "Phenelzine". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID 32119395. Retrieved 2023-11-23.
  6. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Van den Eynde V, Abdelmoemin WR, Abraham MM, Amsterdam JD, Anderson IM, Andrade C, et al. (August 2023). "The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression". CNS Spectrums. 28 (4): 427–440. doi:10.1017/S1092852922000906. PMID 35837681.
  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 from the original (PDF) on 2009-11-27. Retrieved 2009-12-14.
  8. ↑ Van den Eynde V, Parker G, Ruhé HG, Birkenhäger TK, Godet L, Shorter E, et al. (August 2023). "On the Origins of MAOI Misconceptions: Reaffirming their Role in Melancholic Depression". Psychopharmacology Bulletin. 53 (3): 35–54. doi:10.64719/pb.4466. PMC 10434306. PMID 37601082.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  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. "Swapping from one MAOI to another MAOI". PsychoTropical Research.
  19. ↑ Feinberg SS (November 2004). "Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication". Journal of Clinical Psychiatry. 65 (11): 1520–1524. PMID 15554766.
  20. ↑ Gillman PK (November 2018). "A reassessment of the safety profile of monoamine oxidase inhibitors: elucidating tired old tyramine myths". Journal of Neural Transmission. 125 (11): 1707–1717. doi:10.1007/s00702-018-1932-y.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ 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. PMC 11533834. PMID 11775064. S2CID 20655821.
  25. ↑ 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.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ Blough B (July 2008). "Dopamine-releasing agents" (PDF). In Trudell ML, Izenwasser S (eds.). Dopamine Transporters: Chemistry, Biology and Pharmacology. Hoboken [NJ]: Wiley. pp. 305–320. ISBN 978-0-470-11790-3. OCLC 181862653. OL 18589888W.
  30. ↑ 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.
  31. ↑ "Phenelzine". go.drugbank.com. Retrieved 2023-11-23.
  32. ↑ "Phenelzine: Package Insert". Drugs.com. Retrieved 2023-11-23.
  33. ↑ "NARDIL- phenelzine sulfate tablet, film coated" (PDF). DailyMed. Archived (PDF) from the original on 2024-05-20. Retrieved 2024-05-20.
  34. ↑ 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.
  35. ↑ 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.
  36. ↑ 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.
  37. 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. [...] phenelzine (N-amino-phenethylamine, an anxiolytic) [...]
  38. 1 2 "PiHKAL·info". Isomer Design. 4 August 2024. Retrieved 2024-08-12.
  39. ↑ 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.
  40. ↑ 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.
  41. ↑ Dyck LE, Durden DA, Yu PH, Davis BA, Boulton AA (May 1983). "Potentiation of the biochemical effects of beta-phenylethylhydrazine by deuterium substitution". Biochem Pharmacol. 32 (9): 1519–1522. doi:10.1016/0006-2952(83)90475-6. PMID 6860370.
  42. ↑ Dourish CT, Dewar KM, Dyck LE, Boulton AA (1983). "Potentiation of the behavioural effects of the antidepressant phenelzine by deuterium substitution". Psychopharmacology (Berl). 81 (2): 122–125. doi:10.1007/BF00429005. PMID 6415742.
  43. ↑ Dewar KM, Dyck LE, Durden DA, Boulton AA (February 1988). "Involvement of brain trace amines in the behavioural effects of phenelzine". Neurochem Res. 13 (2): 113–119. doi:10.1007/BF00973322. PMID 3362290.
  44. ↑ Dyck LE, Juorio AV, Durden DA, Boulton AA (March 1988). "Effect of chronic deuterated and non-deuterated phenelzine on rat brain monoamines and monoamine oxidase". Naunyn Schmiedebergs Arch Pharmacol. 337 (3): 279–283. doi:10.1007/BF00168839. PMID 3393230.
  45. ↑ Dewar KM, Dyck LE, Durden DA, Boulton AA (July 1988). "Effect of deuterium substitution on the penetration of beta-phenylethylhydrazine into the rat brain". Biochem Pharmacol. 37 (13): 2703–2704. doi:10.1016/0006-2952(88)90266-3. PMID 3390229.
  46. ↑ Yu PH, Tipton KF (December 1989). "Deuterium isotope effect of phenelzine on the inhibition of rat liver mitochondrial monoamine oxidase activity". Biochem Pharmacol. 38 (23): 4245–4251. doi:10.1016/0006-2952(89)90522-4. PMID 2597196.
  47. ↑ Budavari S, O'Neil, Smith A, Heckelman PE, Kinneary JF (1996). "Phenelzine". The Merck Index (12th ed.). Whitehouse Station: Merck & Co. 7181.
  48. ↑ 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.
  49. ↑ 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.
  50. ↑ 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.
  51. ↑ 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.
  52. ↑ 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.
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