Phenelzine (DB00780): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Phenelzine is a potent antidepressant and anxiolytic agent belonging to the hydrazine class of drugs.[1] It functions as a non-selective, irreversible inhibitor of the enzyme monoamine oxidase (MAOI), a mechanism that distinguishes it pharmacologically from nearly all other modern antidepressants.[3] Its primary approved indication is for the treatment of major depressive disorder, particularly in patients with clinical features described as “atypical,” “nonendogenous,” or “neurotic,” and it is often reserved for cases that have proven resistant to other therapies.[5] The profound efficacy of Phenelzine is attributed to its broad-spectrum action, which elevates the synaptic concentrations of the three major monoamine neurotransmitters—serotonin, norepinephrine, and dopamine—while also uniquely increasing levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA).[2]

This therapeutic power is counterbalanced by a complex and demanding safety profile that requires meticulous clinical management. The irreversible nature of its enzyme inhibition necessitates strict adherence to dietary restrictions to prevent a potentially fatal tyramine-induced hypertensive crisis, colloquially known as the "cheese effect".[9] Furthermore, co-administration with a wide range of medications, particularly serotonergic agents, is contraindicated due to the risk of life-threatening serotonin syndrome.[12] Consequently, Phenelzine occupies a specialized niche in psychopharmacology as a highly effective but high-risk agent, representing an invaluable therapeutic option for a select population of patients with severe and treatment-refractory mood and anxiety disorders when prescribed and monitored by experienced clinicians.[14]

Drug Identification and Physicochemical Properties

Phenelzine is a small molecule synthetic organic compound classified as a primary amine and a phenethylamine derivative.[2] It is administered clinically as phenelzine sulfate, a salt form that enhances its stability and formulation properties.[1] The foundational chemical identity and physical characteristics of Phenelzine are summarized in Table 1.

The compound is identified by the Chemical Abstracts Service (CAS) Registry Number 51-71-8 for the free base and 156-51-4 for the sulfate salt.[16] It is known commercially by the brand name Nardil.[3] Its systematic International Union of Pure and Applied Chemistry (IUPAC) name is (2-phenylethyl)hydrazine, reflecting its structure as a hydrazine moiety attached to a phenethyl group.[18]

---

Table 1: Physicochemical and Structural Properties of Phenelzine

Property	Value	Source(s)
Generic Name	Phenelzine	14
Brand Name	Nardil®	3
Synonyms	β-Phenylethylhydrazine, Phenethylhydrazine, (2-Phenylethyl)hydrazine	20
CAS Number (Base)	51-71-8	17
CAS Number (Sulfate)	156-51-4	16
DrugBank ID	DB00780	5
EC Number	200-117-9	14
Molecular Formula	$C_{8}H_{12}N_{2}$ (Base); $C_{8}H_{12}N_{2} \cdot H_{2}SO_{4}$ (Sulfate)	1
Molecular Weight	136.19 g/mol (Base); 234.27 g/mol (Sulfate)	1
SMILES	NNCCc1ccccc1	19
InChIKey	RMUCZJUITONUFY-UHFFFAOYSA-N	19
Melting Point	<25 °C	14
Boiling Point	74 °C at 0.1 Torr	14
Water Solubility (Sulfate)	11.1 mg/mL	16
pKa (Strongest Basic)	5.55	16

---

Preclinical and Clinical Pharmacology

The unique clinical profile of Phenelzine is a direct result of its complex and multifaceted pharmacological actions, which extend beyond its primary mechanism to influence multiple neurotransmitter systems.

Mechanism of Action

The principal mechanism of action of Phenelzine is the potent, non-selective, and irreversible inhibition of monoamine oxidase (MAO).[3] MAO is a critical mitochondrial enzyme responsible for the oxidative deamination and subsequent degradation of monoamine neurotransmitters. It exists in two primary isoforms, MAO-A and MAO-B, both of which are inhibited by Phenelzine with a slight preference for MAO-A.[2]

• MAO-A preferentially metabolizes serotonin and norepinephrine, the two neurotransmitters most closely implicated in the pathophysiology of depression.[4]
• MAO-B preferentially metabolizes dopamine and trace amines such as phenethylamine.[10]

By forming a stable, covalent bond with the flavin cofactor of the MAO enzyme, Phenelzine effectively deactivates it permanently.[10] This irreversible inhibition prevents the breakdown of monoamines within the presynaptic neuron, leading to an accumulation of serotonin, norepinephrine, and dopamine available for vesicular storage and subsequent release into the synaptic cleft.[2] The resulting global increase in the availability of these key neurotransmitters is believed to restore deficient neurochemical signaling and mediate the drug's powerful antidepressant effects.[8]

Beyond this primary mechanism, Phenelzine exerts significant secondary effects. A key metabolite, phenylethylidenehydrazine (PEH), is an inhibitor of γ-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the catabolism of GABA.[2] Inhibition of GABA-T leads to a substantial increase in brain concentrations of GABA, the principal inhibitory neurotransmitter in the central nervous system.[3] This GABA-ergic effect is thought to contribute significantly to Phenelzine's pronounced anxiolytic and antipanic properties, a feature that distinguishes it from many other classes of antidepressants.[2] Phenelzine and its metabolites also inhibit alanine transaminase (ALA-T) to a lesser extent.[2]

Pharmacodynamics

The pharmacodynamic effects of Phenelzine are profound and long-lasting, a direct consequence of its irreversible mechanism. While the drug itself is cleared from the body relatively quickly, its biological effects persist until the body can synthesize new MAO enzymes to replace those that have been permanently inactivated.[2] This process of de novo enzyme synthesis can take up to two to three weeks, creating a significant disconnect between the drug's pharmacokinetic profile and its pharmacodynamic duration of action.[2]

This extended duration of effect is the cornerstone of Phenelzine's clinical and safety considerations. It explains why a therapeutic response may be delayed despite rapid achievement of MAO inhibition and, more critically, why dietary and drug interaction precautions must be maintained for at least 14 days after the last dose.[29] A therapeutic response is typically associated with the inhibition of at least 80-85% of MAO activity.[2] The drug's GABA-elevating action provides a distinct pharmacodynamic advantage in treating depressive disorders with high levels of comorbid anxiety.[2] Conversely, the same powerful modulation of monoamine systems is responsible for the severe adverse reactions seen with interacting substances. The inhibition of ALA-T has been postulated as a potential mechanism for the rare but serious hepatotoxicity associated with hydrazine-class drugs.[2]

Pharmacokinetics (Absorption, Distribution, Metabolism, Excretion)

Phenelzine is administered orally as the sulfate salt and is rapidly absorbed from the gastrointestinal tract.[1] Following a single 30 mg oral dose, a mean peak plasma concentration ($C_{max}$) of 19.8 ng/mL is achieved at a median time to peak ($T_{max}$) of 43 minutes.[1]

The drug undergoes extensive metabolism, primarily through oxidation by monoamine oxidase itself.[1] The major metabolites, phenylacetic acid and parahydroxyphenylacetic acid, are recovered in the urine and account for approximately 73% of an administered dose within 96 hours.[1] Minor metabolic pathways include acetylation to $N^{2}$-acetylphenelzine and conversion to other active metabolites, including phenylethylidenehydrazine (PEH) and phenethylamine (PEA).[2] Unchanged Phenelzine exhibits high protein binding, which may reduce its bioavailability.[26]

The mean elimination half-life ($t_{1/2}$) of Phenelzine is short, approximately 11.6 hours after a single 30 mg dose.[1] This short pharmacokinetic half-life stands in stark contrast to its prolonged pharmacodynamic effect, a critical concept for safe prescribing.

---

Table 2: Summary of Key Pharmacokinetic Parameters

Parameter	Value	Source(s)
Route of Administration	Oral	2
Time to Peak Plasma Concentration ($T_{max}$)	43 minutes	1
Peak Plasma Concentration ($C_{max}$)	19.8 ng/mL (after 30 mg dose)	1
Protein Binding	High	26
Metabolism	Extensive, primarily via oxidation by MAO	1
Major Metabolites	Phenylacetic acid, Parahydroxyphenylacetic acid	1
Elimination Half-Life ($t_{1/2}$)	11.6 hours	1
Route of Excretion	Primarily renal (as metabolites)	1

---

Therapeutic Applications and Clinical Efficacy

Phenelzine's potent and broad mechanism of action translates to high efficacy in specific, often difficult-to-treat psychiatric conditions. Its use has also been explored beyond neuropsychiatry.

Approved Indication: Major Depressive Disorder

Phenelzine is approved by the U.S. Food and Drug Administration (FDA) for the treatment of depression, specifically in patients characterized as “atypical,” “nonendogenous,” or “neurotic”.[5] These presentations of depression are often marked by significant anxiety, phobic or hypochondriacal features, mood reactivity (mood brightens in response to positive events), and reversed vegetative symptoms such as increased appetite and hypersomnia.[26]

Prescribing guidelines explicitly state that Phenelzine should rarely be the first antidepressant used.[7] Instead, it is considered a second- or third-line agent, most suitable for patients who have failed to respond to drugs more commonly used for these conditions, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs).[8] Its established efficacy in treatment-resistant depression makes it a critical tool for a significant subset of the patient population.[15]

Off-Label and Investigational Uses

The clinical utility of Phenelzine extends beyond its approved indication, with substantial evidence supporting its use in a range of other disorders.

• Anxiety Disorders: Phenelzine is recognized as a highly effective treatment for panic disorder and social anxiety disorder.[2] Its unique GABA-elevating properties are believed to confer superior anxiolytic effects compared to other antidepressants, making it a valuable option for patients with severe, debilitating anxiety.[2]
• Eating Disorders: The medication has been used in the management of bulimia nervosa.[2] However, its use in this population requires extreme caution, as patients with binge eating and purging behaviors may be at higher risk for dangerous interactions.[14]
• Other Psychiatric Conditions: The literature also describes its use in treating dysthymia, bipolar depression, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD).[2]
• Oncology Research: The systemic effects of MAO inhibition have prompted investigation of Phenelzine in oncology. A completed Phase 1 clinical trial (NCT03505528) explored its use in combination with paclitaxel for patients with metastatic breast cancer.[36] A separate Phase 2 trial (NCT01253642) investigating Phenelzine with docetaxel in men with advanced prostate cancer was terminated.[37] This exploration into oncology signifies a conceptual expansion of MAO's role beyond neurochemistry into broader cellular biology, positioning MAOIs as potential candidates for drug repurposing, although clinical translation remains challenging.
• Neuroprotection: Preclinical studies have demonstrated that Phenelzine possesses neuroprotective and neurorescue properties, suggesting potential applications in neurodegenerative conditions.[2]

Dosing, Administration, and Clinical Monitoring

The safe and effective use of Phenelzine requires a structured approach to dosing, careful administration protocols, and diligent clinical monitoring.

Dosing and Titration Regimens

• Initial Dose: The usual starting dose for adults is 15 mg taken orally three times per day, for a total of 45 mg daily.[32]
• Dose Titration: The dose should be increased at a fairly rapid pace, consistent with patient tolerance, to at least 60 mg per day. To achieve sufficient MAO inhibition and a clinical response, doses up to 90 mg per day may be necessary.[38] A therapeutic effect may not become apparent until the patient has been on a dose of at least 60 mg daily for a minimum of four weeks.[33]
• Maintenance Dose: After the maximum therapeutic benefit has been achieved (typically within 2-6 weeks), the dosage should be reduced slowly over several weeks to the lowest effective maintenance level. This maintenance dose may be as low as 15 mg daily or every other day.[32]

Administration and Discontinuation Protocols

Phenelzine is administered orally in tablet form.[33] Abrupt discontinuation must be avoided. To prevent withdrawal symptoms—which can include nightmares, agitation, psychosis, nausea, and vomiting—the dose should be tapered gradually when therapy is terminated.[33]

Essential Patient Monitoring

Given the drug's safety profile, regular monitoring is a critical component of treatment.

• Blood Pressure: Blood pressure should be monitored regularly, particularly during dose titration, for signs of postural hypotension.[38] Patients should also be educated on the symptoms of a hypertensive crisis.
• Liver Function: Due to the rare risk of hepatotoxicity, clinicians may consider obtaining baseline and periodic liver function tests.[38]
• Psychiatric Status: In accordance with the FDA Boxed Warning, all patients, especially children, adolescents, and young adults, must be closely monitored for clinical worsening, the emergence of suicidal ideation, or unusual changes in behavior. This monitoring should be most intensive during the initial few months of therapy and following any dose adjustments.[1]

Safety Profile and Risk Management

The clinical use of Phenelzine is defined by its significant safety concerns and the rigorous risk management strategies required to mitigate them.

FDA Boxed Warning: Suicidality

Phenelzine, like other antidepressant medications, carries an FDA-mandated Boxed Warning regarding an increased risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) during the initial months of treatment.[30] Pooled analyses of short-term trials showed that the risk of suicidality in this population was approximately twice as high in those receiving antidepressants compared to placebo (4% vs. 2%).[30] It is critical to note that Phenelzine is not approved for use in pediatric patients.[30] For any patient starting therapy, close observation for clinical worsening, suicidality, or unusual behavioral changes is essential.[1]

Adverse Drug Reactions

Phenelzine is associated with a wide range of adverse effects, from common and manageable to rare and life-threatening. The chemical structure of Phenelzine, a hydrazine derivative, may contribute to some of its idiosyncratic toxicities.[1] The hepatotoxicity profile, for instance, is similar to that of isoniazid, another hydrazine-containing drug, suggesting the hydrazine moiety may act as a toxicophore that, upon hepatic metabolism, generates a reactive intermediate capable of causing hepatocellular injury.[42]

---

Table 3: Common and Serious Adverse Effects Categorized by System Organ Class

System Organ Class	Common (1% to 10%)	Less Common / Rare (<1%)
Psychiatric	Insomnia, hypersomnia, sleep disturbances, anorgasmia, hypomania	Agitation, confusion, euphoria, hallucinations, psychosis, withdrawal syndrome, suicidal ideation 1
Nervous System	Dizziness, headache, drowsiness, tremors, twitching, overactive reflexes	Seizures, nystagmus, paresthesia, ataxia 6
Cardiovascular	Postural hypotension, edema	Arrhythmias, tachycardia, bradycardia, hypertensive crisis 43
Gastrointestinal	Constipation, dry mouth, nausea	Abdominal pain, diarrhea 42
Metabolic	Weight gain	Increased appetite, hypernatremia, metabolic acidosis 42
Genitourinary	Sexual disturbances (impotence, ejaculatory delay, anorgasmia)	Urinary retention, difficulty in micturition 42
Hepatic	Transient elevations in aminotransferases	Severe hepatocellular or cholestatic liver injury, jaundice 42
General	Fatigue, weakness	Jitteriness, fever, malaise 42
Ocular	Blurred vision	Glaucoma, nystagmus, photophobia 43

---

Contraindications and High-Risk Populations

The use of Phenelzine is absolutely contraindicated in patients with [30]:

• Pheochromocytoma
• Congestive heart failure
• A history of liver disease or abnormal liver function tests
• Severe renal impairment or renal disease
• Known hypersensitivity to the drug

Extreme caution is warranted in patients with bipolar disorder (risk of inducing mania), schizophrenia, diabetes, and hypotension.[6] Geriatric patients may be more sensitive to adverse effects and should be started on lower doses with cautious titration.[9]

Critical Interactions and Management

The safe use of Phenelzine is critically dependent on the strict avoidance of numerous drug-food and drug-drug interactions. Patient education is paramount.

Drug-Food Interaction: The Tyramine-Induced Hypertensive Crisis

The most notorious interaction associated with MAOIs is the tyramine-induced hypertensive crisis, or "cheese effect".[10]

• Mechanism: Tyramine is a naturally occurring vasoactive amine found in many aged, fermented, or spoiled foods.[33] Under normal conditions, it is metabolized and inactivated by MAO-A in the intestinal wall and liver.[10] When Phenelzine irreversibly inhibits MAO-A, this metabolic shield is lost. Ingested tyramine is then absorbed systemically, where it acts as a potent indirect sympathomimetic agent, entering adrenergic nerve terminals and triggering a massive, uncontrolled release of stored norepinephrine.[10] This flood of norepinephrine causes extreme vasoconstriction and cardiac stimulation, leading to a rapid and dangerous spike in blood pressure.[45]
• Clinical Manifestations: Symptoms typically appear within one to two hours of ingesting a high-tyramine food and include a severe, throbbing occipital headache that may radiate frontally, neck stiffness, palpitations, chest pain, profuse sweating, nausea, and vomiting.[11] This crisis can lead to intracranial hemorrhage and can be fatal.[29]
• Management: This is a medical emergency. Phenelzine should be discontinued immediately, and therapy to lower blood pressure must be instituted. The recommended agent is a rapid-acting alpha-adrenergic antagonist such as intravenous phentolamine.[31] Patients must be educated to adhere to a low-tyramine diet throughout treatment and for at least 14 days after discontinuing the medication.

---

Table 4: Tyramine Risk Categories in Foods and Beverages

Risk Level	Foods and Beverages to Avoid or Limit	Rationale
High Risk (Avoid Completely)	All aged and mature cheeses (e.g., cheddar, blue, swiss, brie, parmesan); air-dried, fermented, or cured meats (e.g., salami, pepperoni, aged sausage); pickled herring; yeast extracts (e.g., Marmite); sauerkraut; fava bean pods; all draft beers; most red wines.	These foods contain high levels of tyramine (>6 mg per serving) due to aging, fermentation, or protein breakdown processes.29
Moderate Risk (Use with Caution)	Soy sauce, tofu, yogurt, sour cream, chocolate, caffeinated beverages.	These items may contain moderate or variable amounts of tyramine or other vasoactive amines. Excessive consumption should be avoided.32
Low / No Risk (Generally Safe)	Freshly prepared meats, poultry, and fish; fresh fruits and vegetables (except fava bean pods); cottage cheese, cream cheese, processed cheese; pasteurized milk products.	These foods have negligible tyramine content when fresh and properly stored. Spoilage can increase tyramine levels.45

---

Drug-Drug Interaction: Serotonin Syndrome

A second, equally dangerous interaction is serotonin syndrome, a potentially fatal condition caused by excess serotonergic activity in the central nervous system.[12]

• Mechanism: This syndrome occurs when Phenelzine is combined with other drugs that increase serotonin levels, such as SSRIs, SNRIs, tricyclic antidepressants, triptans, dextromethorphan, and certain opioids (e.g., tramadol, fentanyl).[12] The combination of decreased serotonin breakdown (from MAO-A inhibition) and another serotonergic mechanism (e.g., reuptake inhibition) leads to a massive overstimulation of serotonin receptors.[12]
• Clinical Manifestations: The syndrome is characterized by a clinical triad of autonomic hyperactivity (fever, sweating, tachycardia, hypertension), neuromuscular abnormalities (tremor, clonus, myoclonus, hyperreflexia, rigidity), and altered mental status (agitation, confusion, delirium, coma).[12]
• Prevention: Prevention is the key management strategy and relies on the strict avoidance of co-prescribing and adherence to mandatory washout periods. A minimum of 14 days must elapse between stopping Phenelzine and starting a serotonergic agent, and vice versa.[12] Due to the very long half-life of fluoxetine and its active metabolite, a longer washout period of at least 5 weeks is required after stopping fluoxetine before Phenelzine can be initiated.[30]

Other Clinically Significant Drug-Drug Interactions

Phenelzine interacts with numerous other drug classes, requiring careful medication review.

---

Table 5: Major Drug-Drug Interactions, Mechanisms, and Management Recommendations

Interacting Drug Class	Examples	Mechanism of Interaction	Management Recommendation
Serotonergic Agents (SSRIs, SNRIs, TCAs, Triptans)	Fluoxetine, Sertraline, Venlafaxine, Amitriptyline, Sumatriptan	Additive serotonergic effects leading to Serotonin Syndrome	Contraindicated. A washout period of at least 14 days is mandatory (5 weeks for fluoxetine).12
Sympathomimetics (Direct & Indirect)	Pseudoephedrine, Phenylephrine, Amphetamine, Methylphenidate, Cocaine	Potentiation of sympathomimetic effects leading to Hypertensive Crisis	Contraindicated. Avoid use during and for 14 days after MAOI therapy.30
Opioid Analgesics	Meperidine, Tramadol, Fentanyl	Serotonin syndrome; severe, unpredictable potentiation of opioid effects (hyperpyrexia, coma, respiratory depression)	Meperidine is absolutely contraindicated. Use of other opioids is not recommended; if essential, use extreme caution with test doses and close monitoring.1
Anesthetics (General & Local)	Desflurane, Anesthetics with sympathomimetic vasoconstrictors (e.g., epinephrine)	Unpredictable cardiovascular effects (severe hypotension or hypertension)	Contraindicated for elective surgery. Discontinue Phenelzine at least 10 days prior to elective procedures.1
Antihypertensive Agents & Diuretics	Beta-blockers, Thiazide diuretics	Exaggerated hypotensive effects	Use with caution; monitor blood pressure closely.31
Buspirone	Buspirone	Reports of elevated blood pressure	Contraindicated.31
Dextromethorphan	Dextromethorphan (in many OTC cough/cold products)	Potential for serotonin syndrome or psychosis	Contraindicated.31

---

Concluding Clinical Perspective

Phenelzine represents a paradigm of high-efficacy, high-risk pharmacology. It is unequivocally one of the most effective antidepressants ever developed, demonstrating a level of therapeutic power in treatment-resistant depression and severe anxiety disorders that is often unmatched by newer agents.[15] Its broad mechanism, which enhances serotonin, norepinephrine, dopamine, and GABA signaling, provides a comprehensive neurochemical modulation that can produce profound clinical improvement in patients who have failed multiple other treatments.

The historical decline in its use was a direct and rational response to the discovery of its severe and potentially fatal interactions in the mid-20th century, which coincided with the development of safer alternatives.[14] However, the perception of Phenelzine as an archaic and unacceptably dangerous drug is an oversimplification that may deprive deserving patients of a life-changing therapy.[28] With a modern, thorough understanding of its pharmacology, the risks associated with Phenelzine are not arbitrary but predictable and, therefore, manageable.

Successful treatment hinges on three pillars: careful patient selection, comprehensive patient education, and diligent clinical monitoring. When these principles are rigorously applied by an experienced clinician, the risk-benefit calculus shifts decisively in favor of treatment for the appropriate patient. Phenelzine should not be viewed as a drug of last resort, but rather as a specialized and targeted intervention. For the patient with debilitating, treatment-refractory atypical depression or social anxiety, Phenelzine remains an invaluable and, in some cases, irreplaceable therapeutic tool.

Works cited

1. NARDIL - accessdata.fda.gov, accessed October 24, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf
2. Phenelzine - Wikipedia, accessed October 24, 2025, https://en.wikipedia.org/wiki/Phenelzine
3. Definition of phenelzine sulfate - NCI Drug Dictionary - National Cancer Institute, accessed October 24, 2025, https://www.cancer.gov/publications/dictionaries/cancer-drug/def/phenelzine-sulfate
4. MAOI toxicity - LITFL, accessed October 24, 2025, https://litfl.com/maoi-toxicity/
5. Atypical Depression | DrugBank Online, accessed October 24, 2025, https://go.drugbank.com/indications/DBCOND0033164
6. Phenelzine (Nardil) | National Alliance on Mental Illness (NAMI), accessed October 24, 2025, https://www.nami.org/about-mental-illness/treatments/mental-health-medications/types-of-medication/phenelzine-nardil/
7. CENTER FOR DRUG EVALUATION AND RESEARCH - accessdata.fda.gov, accessed October 24, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/011909Orig1s030.pdf
8. Phenelzine Tablets - Cleveland Clinic, accessed October 24, 2025, https://my.clevelandclinic.org/health/drugs/20382-phenelzine-tablets
9. Phenelzine (oral route) - Side effects & dosage - Mayo Clinic, accessed October 24, 2025, https://www.mayoclinic.org/drugs-supplements/phenelzine-oral-route/description/drg-20073198
10. Irreversible Monoamine Oxidase Inhibitors Revisited - Psychiatric Times, accessed October 24, 2025, https://www.psychiatrictimes.com/view/irreversible-monoamine-oxidase-inhibitors-revisited
11. Hypertensive crisis and cheese - PMC - NIH, accessed October 24, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC2738414/
12. Serotonin syndrome induced by transitioning from phenelzine to venlafaxine: Four patient reports - Neurology.org, accessed October 24, 2025, https://www.neurology.org/doi/10.1212/WNL.51.1.274
13. Sertraline-phenelzine drug interaction: a serotonin syndrome reaction - PubMed, accessed October 24, 2025, https://pubmed.ncbi.nlm.nih.gov/7919561/
14. 51-71-8 | CAS DataBase - ChemicalBook, accessed October 24, 2025, https://m.chemicalbook.com/CASEN_51-71-8.htm
15. The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression | CNS Spectrums - Cambridge University Press & Assessment, accessed October 24, 2025, https://www.cambridge.org/core/journals/cns-spectrums/article/prescribers-guide-to-classic-mao-inhibitors-phenelzine-tranylcypromine-isocarboxazid-for-treatmentresistant-depression/29C70FD3DA65E23A024D5E05C4369983
16. Phenelzine sulfate | DrugBank Online, accessed October 24, 2025, https://go.drugbank.com/salts/DBSALT000954
17. Phenelzine and its acid salts - OEHHA - CA.gov, accessed October 24, 2025, https://oehha.ca.gov/proposition-65/chemicals/phenelzine-and-its-acid-salts
18. Substance Information - ECHA - European Union, accessed October 24, 2025, https://echa.europa.eu/substance-information/-/substanceinfo/100.000.108
19. Phenelzine | C8H12N2 | CID 3675 - PubChem - NIH, accessed October 24, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Phenelzine
20. Phenethyl-hydrazine | CAS 51-71-8 | SCBT - Santa Cruz Biotechnology, accessed October 24, 2025, https://www.scbt.com/p/phenethyl-hydrazine-51-71-8
21. Phenelzine - CAS Common Chemistry, accessed October 24, 2025, https://commonchemistry.cas.org/detail?cas_rn=51-71-8&search=51-71-8
22. phenelzine | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY, accessed October 24, 2025, https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=clinical&ligandId=7266
23. www.mayoclinic.org, accessed October 24, 2025, https://www.mayoclinic.org/drugs-supplements/phenelzine-oral-route/description/drg-20073198#:~:text=Phenelzine%20is%20used%20to%20treat,MAO)%20in%20the%20nervous%20system.%2520in%2520the%2520nervous%2520system.&sa=D&source=editors&ust=1761302367834750&usg=AOvVaw0qNEBerU1rneF-f3u9x46k)
24. What is the mechanism of Phenelzine Sulfate? - Patsnap Synapse, accessed October 24, 2025, https://synapse.patsnap.com/article/what-is-the-mechanism-of-phenelzine-sulfate
25. MAOIs with a Focus on Phenelzine - Philadelphia Integrative Psychiatry, accessed October 24, 2025, https://phillyintegrative.com/blog/maois-for-severe-depression
26. Phenelzine: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed October 24, 2025, https://go.drugbank.com/drugs/DB00780
27. Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine, accessed October 24, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8732914/
28. The role of classic Monoamine Oxidase Inhibitors in treatment-resistant depression: proposal for the inclusion of Phenelzine in the Complementary List of Essential Medicines - World Health Organization (WHO), accessed October 24, 2025, https://cdn.who.int/media/docs/default-source/essential-medicines/2023-eml-expert-committee/applications-for-addition-of-new-medicines/a32_phenelzine.pdf?sfvrsn=8410066c_2
29. Phenelzine and Alcohol/Food Interactions - Drugs.com, accessed October 24, 2025, https://www.drugs.com/food-interactions/phenelzine.html
30. NARDIL - accessdata.fda.gov, accessed October 24, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s036lbl.pdf
31. nardil | fda, accessed October 24, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/11909slr033_nardil_lbl.pdf
32. PHENELZINE SULFATE TABLETS, USP Novel Laboratories, Inc. Rx Only - DailyMed, accessed October 24, 2025, https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=b7ec6ae7-3d76-42aa-9d8a-fc3e187769b5
33. Phenelzine: MedlinePlus Drug Information, accessed October 24, 2025, https://medlineplus.gov/druginfo/meds/a682089.html
34. pubchem.ncbi.nlm.nih.gov, accessed October 24, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Phenelzine#:~:text=Phenelzine%2C%20with%20the%20formula%20%CE%B2,approved%20on%20June%209th%2C%201961.
35. Nardil - Drug Summary - PDR.Net, accessed October 24, 2025, https://www.pdr.net/drug-summary/nardil-phenelzine-sulfate-462
36. Phenelzine Completed Phase 1 Trials for Metastatic Breast Cancer Treatment - DrugBank, accessed October 24, 2025, https://go.drugbank.com/drugs/DB00780/clinical_trials?conditions=DBCOND0030200&phase=1&purpose=treatment&status=completed
37. Phenelzine Terminated Phase 2 Trials for Metastatic Prostate Adenocarcinoma / Adenocarcinoma of Prostate / Recurrent Prostate Carcinoma / Hormone Resistant Prostate Cancer Treatment - DrugBank, accessed October 24, 2025, https://go.drugbank.com/drugs/DB00780/clinical_trials?conditions=DBCOND0031670%2CDBCOND0038482%2CDBCOND0112425%2CDBCOND0030423&phase=2&purpose=treatment&status=terminated
38. Phenelzine Dosage Guide + Max Dose, Adjustments - Drugs.com, accessed October 24, 2025, https://www.drugs.com/dosage/phenelzine.html
39. Nardil Dosage Guide - Drugs.com, accessed October 24, 2025, https://www.drugs.com/dosage/nardil.html
40. Nardil (phenelzine) dosing, indications, interactions, adverse effects, and more, accessed October 24, 2025, https://reference.medscape.com/drug/nardil-phenelzine-342951
41. Phenelzine Monograph for Professionals - Drugs.com, accessed October 24, 2025, https://www.drugs.com/monograph/phenelzine.html
42. Phenelzine - LiverTox - NCBI Bookshelf - NIH, accessed October 24, 2025, https://www.ncbi.nlm.nih.gov/books/NBK548402/
43. Phenelzine Side Effects: Common, Severe, Long Term - Drugs.com, accessed October 24, 2025, https://www.drugs.com/sfx/phenelzine-side-effects.html
44. Phenelzine (Nardil): Uses, Side Effects, Dosage & More - GoodRx, accessed October 24, 2025, https://www.goodrx.com/phenelzine/what-is
45. Dietary Restrictions and Drug Interactions With Monoamine Oxidase Inhibitors: An Update, accessed October 24, 2025, https://www.psychiatrist.com/jcp/dietary-restrictions-drug-interactions-monoamine-oxidase-update-maoi/
46. Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors. - Scholarly Commons, accessed October 24, 2025, https://scholarlycommons.pacific.edu/cgi/viewcontent.cgi?article=1663&context=phs-facarticles
47. Monoamine Oxidase Inhibitor (MAOI) Toxicity - Emergency Management - DynaMed, accessed October 24, 2025, https://www.dynamed.com/management/monoamine-oxidase-inhibitor-maoi-toxicity-emergency-management
48. Phenelzine Sulfate Food, Alcohol, Supplements and Drug Interactions - ScriptSave WellRx, accessed October 24, 2025, https://www.wellrx.com/phenelzine-sulfate/lifestyle-interactions/
49. Serotonin syndrome - Symptoms & causes - Mayo Clinic, accessed October 24, 2025, https://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes/syc-20354758
50. NEW ZEALAND DATA SHEET - Medsafe, accessed October 24, 2025, https://www.medsafe.govt.nz/Profs/Datasheet/n/Nardiltab.pdf