Phenelzine Chemical Properties

Melting point:

25°C

Boiling point:

bp0.1 74°

Density 

1.0348 (rough estimate)

refractive index 

nD20 1.5494

pka

8.01±0.70(Predicted)

CAS DataBase Reference

51-71-8(CAS DataBase Reference)

NIST Chemistry Reference

Hydrazine, (2-phenylethyl)-(51-71-8)

EPA Substance Registry System

Phenelzine (51-71-8)

Safety Information

Hazard Codes 

Xi

HazardClass 

IRRITANT

Hazardous Substances Data

51-71-8(Hazardous Substances Data)

Toxicity

LD50 oral in mouse: 130mg/kg

Phenelzine Usage And Synthesis

Description

Monoamine oxidase inhibitors (MAOIs) were the first antidepressant drugs introduced during the 1950s. Associated with many side effects and, in particular, drug–drug and drug–food interactions, their use declined with the subsequent introduction of the tricyclic antidepressants and specific serotonin reuptake inhibitors as first-line treatments for depression.

Originator

Nardil ,Parke Davis, US ,1959

Uses

Antidepressant.

Uses

MAOIs are used to treat atypical and refractory depression. They have also been used in the treatment of panic attacks, narcolepsy, and bulimia. Selective monoamine oxidase B (MAO-B) inhibitors such as selegiline are used to treat Parkinson’s disease.

Uses

Phenelzine is a MAO inhibitor which is used for treating patients with depressive characteristics such as “atypical,” “nonendogenous,” or “neurotic” conditions in which a combination of anxiety, depression, or phobia are observed. Phenelzine is not a drug of first choice, and it is used in depressions that do not respond to other medicinal drugs.

Definition

ChEBI: Phenelzine is a primary amine.

Manufacturing Process

To a refluxing solution containing 147.5 grams of 85% hydrazine hydrate in 500 cc of ethanol was added, during a period of 5 hours, 92.5 grams of phenethylbromide (0.50 mol) in 150 cc of ethanol. Stirring and refluxing were continued for two hours. The ethanol was removed by distillation and the residue extracted repeatedly with ether. The ether was dried with potassium carbonate and the product base collected by distillation, BP 74°C/0.1 mm, yield 52.3 grams (77%). The base is reacted with sulfuric acid in propanol to give the sulfate.

brand name

Nardil (Parke-Davis).

Therapeutic Function

Psychostimulant

Mechanism of action

Phenelzine is a hydrazine MAOI. Its mechanism of action is the prolonged, nonselective, irreversible inhibition of MAO. Phenelzine has been used with some success in the management of bulimia nervosa. The MAOIs, however, are potentially dangerous in patients with binge eating and purging behaviors, and the American Psychiatric Association states that MAOIs should be used with caution in the management of bulimia nervosa.

Clinical Use

MAOI antidepressant

Safety Profile

Poison by ingestion, intraperitoneal, and subcutaneous routes. Human systemic effects by ingestion: ataxia, somnolence. An experimental teratogen. Experimental reproductive effects. Mutation data reported. Used as an antidepressant. When heated to decomposition it emits toxic fumes of NOx.

Synthesis

Phenelzine, 2-phenylethylhydrazine (7.2.1), is synthesized by reacting 2-phenylethylbromide with hydrazine [42¨C45].

Drug interactions

Potentially hazardous interactions with other drugs
Alcohol: some alcoholic and dealcoholised drinks contain tyramine which can cause hypertensive crisis.
Alpha-blockers: avoid with indoramin; enhanced hypotensive effect.
Analgesics: CNS excitation or depression with pethidine, other opioids and nefopam - avoid; increased risk of serotonergic effects and convulsions with tramadol - avoid.
Antidepressants: enhancement of CNS effects and toxicity. Care with all antidepressants including drug free periods when changing therapies.
Antiepileptics: antagonism of anticonvulsant effect; avoid carbamazepine with or within 2 weeks of MAOIs.
Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol.
Antipsychotics: effects enhanced by clozapine.
Atomoxetine: avoid concomitant use and for 2 weeks after use.
Bupropion: avoid with or for 2 weeks after MAOIs.
Dapoxetine: risk of hypertensive crisis - avoid.
Diuretics: avoid with indoramin.
Dopaminergics: avoid with entacapone and tolcapone; hypertensive crisis with levodopa and rasagiline - avoid for at least 2 weeks after stopping MAOI; hypotension with selegiline.
5HT1 agonist: risk of CNS toxicity with sumatriptan, rizatriptan and zolmitriptan - avoid sumatriptan and rizatriptan for 2 weeks after MAOI.
Methyldopa: avoid concomitant use.
Opicapone: avoid concomitant use.
Sympathomimetics: hypertensive crisis with sympathomimetics - avoid with methylphenidate.
Tetrabenazine: risk of CNS excitation and hypertension avoid.

Environmental Fate

MAOIs are available orally. Accidental or intentional ingestion are the most common routes of exposure.

Metabolism

Phenelzine is metabolised in the liver by oxidation via monoamine oxidase, and is excreted in the urine almost entirely in the form of metabolites.

Toxicity evaluation

Monoamine oxidase is the enzyme principally responsible for degradation of amine neurotransmitters (norepinephrine, epinephrine, serotonin, and dopamine). There are two isoenzymes of monoamine oxidase: monoamine oxidase A (MAO-A) and MAO-B. MAO-A preferentially deaminates serotonin, norepinephrine, and epinephrine as well as dietary vasopressors such as tyramine. MAO-B preferentially deaminates dopamine and phenethylamine. MAOIs block the monoamine oxidase enzymes leading to neurotransmitter accumulation. The older MAOIs such as phenelzine, tranylcypromine, and isocarboxazid were irreversible and nonselective and inhibited both MAO-A and MAO-B. Moclobemide is a reversible MAO-A inhibitor used in the treatment of depression. Selegiline and rasagiline are irreversible selective MAO-B inhibitors and are approved to treat Parkinson’s disease. MAOIs do not have any effect on monoamine oxidase production. Once irreversibly blocked, the monoamine oxidase enzyme level then regenerates over many weeks. MAOIs may also stimulate the release of norepinephrine from some nerve endings while having a sympatholytic effect at postganglionic terminals. Since selegiline is MAO-B selective, its use does not result in as many drug–drug and drug–food interactions as the other MAOIs.

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