Phenelzine
- CAS NO.:51-71-8
- Empirical Formula: C8H12N2
- Molecular Weight: 136.19
- MDL number: MFCD00047825
- EINECS: 200-117-9
- SAFETY DATA SHEET (SDS)
- Update Date: 2024-03-28 13:39:29
What is Phenelzine?
Absorption
Phenelzine is rapidly absorbed from the gastrointestinal tract. The decay of the drug action is not dependent on the pharmacokinetic parameters but on the rate of protein synthesis which restores the functional levels of monoamine oxidase. The mean Cmax is 19.8 ng/ml and it occurs after 43 minutes of dose administration.
Toxicity
Phenelzine, as must of the monoamine oxidase inhibitors, can cause transient, mild and asymptomatic aminotransferase elevations. It has also been reported to be associated with cases of liver injury after 1-3 months of treatment.
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
The Uses of Phenelzine
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.
The Uses of Phenelzine
Antidepressant.
The Uses of Phenelzine
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.
Indications
Phenelzine is indicated for the treatment of nonendogenous, neurotic or atypical depression for patients that do not tolerate other forms of therapy.
Atypical depression has a high prevalence rate, starts in early life, tends to last longer, is more likely to occur in people with bipolar disorder, has a high comorbidity with anxiety disorder and carries more risk of suicidal behavior. It is important to specify the atypical feature to predict the clinical course of depression and hence generate the best treatment and service. The featuring symptoms of the atypical feature include mood reactivity, two or more of this symptoms: 1) increased appetite, 2) increased sleep, 3) leaden paralysis and 4) interpersonal rejection sensitivity and should not have melancholic or catatonic features of depression.
Neurotic depression is a depression of an emotionally unstable person. It is a secondary condition to major personality disorder, neuroses and drug use disorders. Likewise, a primary depression with a family history of depression spectrum disease would fit in this category.
A nonendogenous depression is characterized by a disturbance in mood and general outlook. The physical symptoms tend to be less severe and it often occurs in response to stressful life events that keep occurring over a large period of time generating a continuous stress in the daily living.
What are the applications of Application
Phenethyl-hydrazine is a biochemical used for proteomics research
Background
Phenelzine, with the formula β-phenylethylhydrazine, is a monoamine oxidase inhibiting antidepressant that is effective in the treatment of panic disorder and social anxiety disorder. It was developed by Parke Davis and originally FDA approved on June 9th, 1961. It is currently approved under prescription by the name of Nardil.
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.
Pharmacokinetics
The elimination of monoamine oxidase by phenelzine results in the elevation of brain amines such as 2-phenylethylamine which is a metabolite of phenelzine. These amines have then marked effects on the uptake and release of catecholamines and serotonin in nerve endings. Phenelzine is shown to elevate brain levels of the gamma-aminobutyric acid (GABA) and alanine (ALA) as well as to inhibit the activity of the transaminases that normally metabolize these amino acids. In preclinical studies, it has been shown to be neuroprotective in cerebral ischemia.
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
For the metabolic studies, it is assumed that phenelzine is acetylated. Some of the metabolites of phenelzine are phenylacetic acid, 2-phenylethylamine and 4-hydroxyphenylacetic acid as major metabolites and N-acetyl-phenelzine as a minor metabolite.
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.
Properties of Phenelzine
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 for Phenelzine
Signal word | Warning |
Pictogram(s) |
Health Hazard GHS08 |
GHS Hazard Statements |
H341:Germ cell mutagenicity |
Precautionary Statement Codes |
P201:Obtain special instructions before use. P202:Do not handle until all safety precautions have been read and understood. P280:Wear protective gloves/protective clothing/eye protection/face protection. P308+P313:IF exposed or concerned: Get medical advice/attention. P405:Store locked up. |
Computed Descriptors for Phenelzine
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