Phenelzine
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Phenelzine
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| Systematic (IUPAC) name | |
| 2-hydrazinylethylbenzene | |
| Identifiers | |
| CAS number | 51-71-8 |
| ATC code | N06AF03 |
| PubChem | 3675 |
| DrugBank | APRD00099 |
| Chemical data | |
| Formula | C8H12N2 |
| Mol. weight | 136.194 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | Liver |
| Half life | 11 hours |
| Excretion | Urine |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status | |
| Routes | Oral |
Phenelzine (sold as Nardil®) is a monoamine oxidase inhibitor (MAOI) used as an antidepressant drug.
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[edit] Mode of action
Phenelzine is a derivative of hydrazine, which is phenylethylamine-like moiety and similar to normal substrates of MAO. When MAO tries to oxidize phenelzine, this hydrazine-moiety binds covalently to the enzyme, thus inactivating it irreversibly. Phenelzine is a non-selective MAO-inhibitor, it inhibits both MAO-A and MAO-B. Furthermore, primarily through its primary metabolite, PEH (phenylethylidenehydrazine), phenelzine elevates levels of GABA in the caudate-putamen and nucleus accumbens. This may contribute to its anxiolytic properties and superior efficiacy in treating severe anxiety.
[edit] Pharmacokinetics
Phenelzine is administered orally as phenelzine sulphate and it is rapidly absorbed from the gastro-intestinal tract. Although phenelzine has a fairly short half-life, its effect lasts for several weeks, until new functional MAO-enzymes have been produced by the body. Phenelzine is acetylated in the liver and its metabolites are excreted in the urine.
[edit] Side effects
Common side effects include orthostatic hypotension, dizziness, headache, fatigue, insomnia, sexual difficulty, hesitant urination, rash, and gastro-intestinal disturbances. Phenelzine can cause, though rarely, severe hepatotoxicity, most likely due to its hydrazine group.
As with other MAOIs, tyramine-containing foods can cause a Cheese syndrome, which is a severe hypertensive crisis, so users of phenelzine must adhere to rigid dietary guidelines. This hypertensive crisis is characterised by severe headache and rapid rise in blood pressure, which can cause cardiac failure and intracranial hemorrhage.
In addition, the intake of a large amount of tryptophan may induce hypomania or other symptoms of serotonin syndrome.
[edit] Nardil formulation
Nardil was changed in late 2003, due to a complete reformulation by Pfizer, who removed many of the excipient ingredients, including the hard coating. It is possible that the current version is not surviving the stomach acid content and therefore not as much is being absorbed into the bloodstream. It is also possible that the machinery used to mix and manufacture Nardil is, since Pfizer acquired the medication, not able to sufficiently blend and mix the medication, making parts or all of some lots irregular in the content of medication delivered to the system.
Many users continue to experience difficulties following this change. The indicated dosage has not been altered by Pfizer, nor did they advise physicians or pharmacies of these changes, yet the recommended dosage seems not to have the desired effect on many. It is believed that, currently, there are some 75,000 to 85,000 people taking Nardil worldwide. The original formulation of Nardil is no longer available.
[edit] Indicated for
Indicated for:
- anxiety disorder
- atypical depression
- bulimia
- refractory depression
- social phobia
