Phenelzine
Encyclopedia
Phenelzine is a non-selective
and irreversible monoamine oxidase inhibitor
(MAOI) of the hydrazine
class which is used as an antidepressant
and anxiolytic
. Along with tranylcypromine
and isocarboxazid
, phenelzine is one of the few non-selective MAOIs still in widespread clinical use.
of major depressive disorder (MDD). Patients with depressive symptomology characterized as "atypical", "nonendogenous", and/or "neurotic", have been reported to respond particularly well to phenelzine. The medication has also been found to be useful in patients who do not respond favorably to first and second-line treatments for depression, or are said to be "treatment-resistant". In addition to being a recognized treatment for major depressive disorder, phenelzine has been found in studies to be effective in treating dysthymia, bipolar depression (BD), panic disorder
(PD), social anxiety disorder
(SAD), bulimia, and post-traumatic stress disorder
(PTSD).
monoamine oxidase
(MAO). It inhibits both of the respective isoforms of MAO, MAO-A and MAO-B, and does so almost equally, with slight preference for the former. By inhibiting MAO, phenelzine prevents the breakdown of the monoamine neurotransmitter
s serotonin
, melatonin
, norepinephrine
, epinephrine
, and dopamine
, as well as the trace amine
neuromodulators such as phenethylamine
, tyramine
, octopamine
, and tryptamine
. This leads to an increase in the extracellular
concentration
s of these neurochemical
s and therefore an alteration in neurochemistry
and subsequently neurotransmission
. It is this action that is thought to be the primary mediator in phenelzine's therapeutic benefits.
Notably, although phenelzine inhibits the breakdown of norepinephrine
and epinephrine
(which in concept should lead to increased levels of these two respective neurotransmitters), it actually typically significantly decreases their overall activity with time via a complex interaction with octopamine
. This is the cause of the side effect of orthostatic hypotension
commonly seen with phenelzine and the other MAOIs. Importantly, it has been demonstrated that the antidepressant effects of serotonin
are actually mediated through norepinephrine. As a result, this depletion of norepinephrine and epinephrine may significantly inhibit the full therapeutic potential of phenelzine and the other MAOIs. For this reason, augmenting with an adrenergic
agent such as a norepinephrine reuptake inhibitor
(NRI) or releasing agent
(NRA) in conjunction may be desirable, though strict professional supervision is advised to minimize the risk of a potentially dangerous drug interaction such as hypertensive crisis.
Phenelzine and its metabolites also inhibit at least two other enzymes to a lesser extent, of which are alanine transaminase
(ALA-T), and γ-Aminobutyric acid transaminase
(GABA-T), the latter of which is not caused by phenelzine itself, but by a phenelzine metabolite phenylethylidenehydrazine
(PEH). By inhibiting ALA-T and GABA-T, phenelzine causes an increase in the alanine
and GABA
levels in the brain and body. GABA is the major inhibitory neurotransmitter in the mammalian central nervous system
, and is very important for the normal suppression of anxiety and stress, as well as keeping depression at bay. It is thought that phenelzine's action in increasing GABA concentrations may significantly contribute to its antidepressant, and especially, anxiolytic/antipanic properties, the latter of which have typically 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
.
Phenelzine has also been shown to metabolize to phenethylamine (PEA). PEA acts as a releasing agent
of norepinephrine and dopamine, and produces effects very similar to those of amphetamine
, though with markedly different pharmacokinetics such as a far shorter duration of action. Phenelzine's enhancement of PEA levels may contribute further to its overall antidepressant effects to some degree. In addition, phenethylamine is a substrate for MAO-B, and treatment with MAOIs that inhibit MAO-B such as phenelzine have been shown to consistently and significantly elevate its concentrations.
Like many other antidepressants, phenelzine usually requires several weeks of treatment to achieve full therapeutic effects. The reason for this delay has not fully been elucidated, but it is believed to be due to many factors, including achieving steady-state levels of MAO inhibition and the resulting adaptations in mean neurotransmitter levels, as well as the possibility of necessary desensitization of autoreceptor
s which normally inhibit the release of neurotransmitters like serotonin and dopamine. Typically, a therapeutic response to MAOIs is believed to be associated with an inhibition of at least 80-85% of monoamine oxidase activity.
. Time to peak plasma concentration is 43 minutes and half-life is 11.6 hours. Unlike most other drugs, phenelzine irreversibly disables MAO, and as a result, 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 actually wear off until the body replenishes its enzyme stores, a process which can take as long as 2–3 weeks.
Phenelzine is metabolized primarily in the liver and its metabolite
s are excreted in the urine. Oxidation is the primary routine 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 the course of 96 hours after single doses. Acetylation to N2-acetylphenelzine is a minor pathway. Phenelzine may also interact with cytochrome P450 enzymes, inactivating these enzymes through formation of a heme adduct. Two other minor metabolites of phenelzine, as mentioned above, include phenylethylidenehydrazine and phenethylamine.
with hydrazine
.
, blurry vision, dry mouth, headache
, lethargy, sedation
, somnolence
, insomnia
, anorexia
, weight gain
or loss
, nausea
and vomiting
, diarrhea
, constipation
, urinary retention
, mydriasis
, muscle tremors, hyperthermia
, sweating
, hypertension
or hypotension
, orthostatic hypotension
, paresthesia
, hepatitis
, and sexual dysfunction
(consisting of loss of libido
and anorgasmia
). Rare side effects usually only seen in susceptible individuals may include hypomania
or mania
, psychosis
, and acute liver failure, the latter of which is usually only seen in people with pre-existing liver damage, old age
, alcohol consumption
, or viral infection.
-containing foods. As a result, patients on phenelzine and other MAOIs must avoid excess quantities of certain foods that contain tyramine such as aged cheeses and cured meats, among others. Serotonin syndrome
may result from an interaction with certain drugs which increase serotonin activity such as selective serotonin reuptake inhibitors and pethidine
(known as meperidine in the US). Several deaths have been reported due to drug interaction-related serotonin syndrome
such as the case of Libby Zion.
As is the case with other MAOIs there is a concern regarding Phenelzine and the use of anesthetics, both Local
and General anesthetic
. Anyone taking Phenelzine should inform their Psychiatrist before proceeding with dental surgery, and surgery in any other contexts. See the MAOI page for further information on this particular concern.
Phenelzine has also been linked to vitamin B6
deficiency. It reacts with vitamin B6 via an unknown enzyme to form a biologically inert metabolite. Both phenelzine and vitamin B6 are rendered inactive upon this reaction occurring. For this reason, it is recommended to supplement with vitamin B6 while taking phenelzine. High doses of vitamin B6 may significantly lower phenelzine levels and subsequently inhibit its therapeutic benefits, however, and thus, excess quantities of vitamin B6 should be avoided. It may be advisable to dose them separately during opposite intervals of the day (e.g., take one, then take the other 12 hours later) to avoid interaction as much as possible.
Binding selectivity
Binding selectivity refers to the differing affinities with which different ligands bind to a substrate forming a complex. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate...
and irreversible monoamine oxidase inhibitor
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
(MAOI) of the hydrazine
Hydrazine
Hydrazine is an inorganic compound with the formula N2H4. It is a colourless flammable liquid with an ammonia-like odor. Hydrazine is highly toxic and dangerously unstable unless handled in solution. Approximately 260,000 tons are manufactured annually...
class which is used as an antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
and anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
. Along with tranylcypromine
Tranylcypromine
Tranylcypromine is a drug of the substituted phenethylamine and amphetamine classes which acts as a monoamine oxidase inhibitor —it is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase...
and isocarboxazid
Isocarboxazid
Isocarboxazid is an irreversible and nonselective monoamine oxidase inhibitor of the hydrazine chemical class used as an antidepressant and anxiolytic...
, phenelzine is one of the few non-selective MAOIs still in widespread clinical use.
Indications
Phenelzine is used primarily in the treatmentTherapy
This is a list of types of therapy .* Adventure therapy* Animal-assisted therapy* Aquatic therapy* Aromatherapy* Art and dementia* Art therapy* Authentic Movement* Behavioral therapy* Bibliotherapy* Buteyko Method* Chemotherapy...
of major depressive disorder (MDD). Patients with depressive symptomology characterized as "atypical", "nonendogenous", and/or "neurotic", have been reported to respond particularly well to phenelzine. The medication has also been found to be useful in patients who do not respond favorably to first and second-line treatments for depression, or are said to be "treatment-resistant". In addition to being a recognized treatment for major depressive disorder, phenelzine has been found in studies to be effective in treating dysthymia, bipolar depression (BD), panic disorder
Panic disorder
Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
(PD), social anxiety disorder
Social anxiety disorder
Social anxiety disorder , also known as social phobia, is an anxiety disorder characterized by intense fear in social situations causing considerable distress and impaired ability to function in at least some parts of daily life...
(SAD), bulimia, and post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...
(PTSD).
Pharmacodynamics
Phenelzine is a non-selective and irreversible inhibitor of the enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
(MAO). It inhibits both of the respective isoforms of MAO, MAO-A and MAO-B, and does so almost equally, with slight preference for the former. By inhibiting MAO, phenelzine prevents the breakdown of the monoamine neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
, and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, as well as the trace amine
Trace amine
Trace amines are endogenous compounds structurally related to classical biogenic amines, such as catecholamines, serotonin and histamine. Trace amines include p-tyramine, β-phenylethylamine, tryptamine, octopamine, and 3-iodothyronamine, and are found in the nervous systems of animals from insects...
neuromodulators such as phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...
, tyramine
Tyramine
Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...
, octopamine
Octopamine
Octopamine is an endogenous biogenic amine that is closely related to norepinephrine, and has effects on the adrenergic and dopaminergic systems. It is also found naturally in numerous plants, including bitter orange. Biosynthesis of the D--enantiomer of octopamine is by β-hydroxylation of...
, and tryptamine
Tryptamine
Tryptamine is a monoamine alkaloid found in plants, fungi, and animals. It is based around the indole ring structure, and is chemically related to the amino acid tryptophan, from which its name is derived...
. This leads to an increase in the extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...
s of these neurochemical
Neurochemical
A neurochemical is an organic molecule, such as serotonin, dopamine, or nerve growth factor, that participates in neural activity. The science of neurochemistry studies the functions of neurochemicals.-Prominent neurochemicals:...
s and therefore an alteration in neurochemistry
Neurochemistry
Neurochemistry is the specific study of neurochemicals, which include neurotransmitters and other molecules such as neuro-active drugs that influence neuron function. This principle closely examines the manner in which these neurochemicals influence the network of neural operation...
and subsequently neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
. It is this action that is thought to be the primary mediator in phenelzine's therapeutic benefits.
Notably, although phenelzine inhibits the breakdown of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
and epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
(which in concept should lead to increased levels of these two respective neurotransmitters), it actually typically significantly decreases their overall activity with time via a complex interaction with octopamine
Octopamine
Octopamine is an endogenous biogenic amine that is closely related to norepinephrine, and has effects on the adrenergic and dopaminergic systems. It is also found naturally in numerous plants, including bitter orange. Biosynthesis of the D--enantiomer of octopamine is by β-hydroxylation of...
. This is the cause of the side effect of orthostatic hypotension
Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...
commonly seen with phenelzine and the other MAOIs. Importantly, it has been demonstrated that the antidepressant effects of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
are actually mediated through norepinephrine. As a result, this depletion of norepinephrine and epinephrine may significantly inhibit the full therapeutic potential of phenelzine and the other MAOIs. For this reason, augmenting with an adrenergic
Adrenergic
An adrenergic agent is a drug, or other substance, which has effects similar to, or the same as, epinephrine . Thus, it is a kind of sympathomimetic agent...
agent such as a norepinephrine reuptake inhibitor
Norepinephrine reuptake inhibitor
A norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
(NRI) or releasing agent
Releasing agent
A releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...
(NRA) in conjunction may be desirable, though strict professional supervision is advised to minimize the risk of a potentially dangerous drug interaction such as hypertensive crisis.
Phenelzine and its metabolites also inhibit at least two other enzymes to a lesser extent, of which are alanine transaminase
Alanine transaminase
Alanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
(ALA-T), and γ-Aminobutyric acid transaminase
4-aminobutyrate aminotransferase
4-aminobutyrate aminotransferase is an enzyme which catalyzes the conversion of 4-aminobutanoic acid and 2-oxoglutarate into succinic semialdehyde and glutamate.-Inhibitors:* Aminooxyacetic acid* Gabaculine* Phenelzine...
(GABA-T), the latter of which is not caused by phenelzine itself, but by a phenelzine metabolite phenylethylidenehydrazine
Phenylethylidenehydrazine
Phenylethylidenehydrazine is an inhibitor of the enzyme GABA transaminase . It is a metabolite of the antidepressant phenelzine and is responsible for its elevation of GABA concentrations. PEH likely plays a significant role in phenelzine's high efficacy in treating anxiety disorders....
(PEH). By inhibiting ALA-T and GABA-T, phenelzine causes an increase in the alanine
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
and GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
levels in the brain and body. GABA is the major inhibitory neurotransmitter in the mammalian central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
, and is very important for the normal suppression of anxiety and stress, as well as keeping depression at bay. It is thought that phenelzine's action in increasing GABA concentrations may significantly contribute to its antidepressant, and especially, anxiolytic/antipanic properties, the latter of which have typically 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
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
and liver failure
Liver failure
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
.
Phenelzine has also been shown to metabolize to phenethylamine (PEA). PEA acts as a releasing agent
Releasing agent
A releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...
of norepinephrine and dopamine, and produces effects very similar to those of amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
, though with markedly different pharmacokinetics such as a far shorter duration of action. Phenelzine's enhancement of PEA levels may contribute further to its overall antidepressant effects to some degree. In addition, phenethylamine is a substrate for MAO-B, and treatment with MAOIs that inhibit MAO-B such as phenelzine have been shown to consistently and significantly elevate its concentrations.
Like many other antidepressants, phenelzine usually requires several weeks of treatment to achieve full therapeutic effects. The reason for this delay has not fully been elucidated, but it is believed to be due to many factors, including achieving steady-state levels of MAO inhibition and the resulting adaptations in mean neurotransmitter levels, as well as the possibility of necessary desensitization of autoreceptor
Autoreceptor
An autoreceptor is a receptor located on presynaptic nerve cell membranes and serves as a part of a feedback loop in signal transduction. It is sensitive only to those neurotransmitters or hormones that are released by the neuron in whose membrane the autoreceptor sits.Canonically, a presynaptic...
s which normally inhibit the release of neurotransmitters like serotonin and dopamine. Typically, a therapeutic response to MAOIs is believed to be associated with an inhibition of at least 80-85% of monoamine oxidase activity.
Pharmacokinetics
Phenelzine is administered orally in the form of phenelzine sulfate and is rapidly absorbed from the gastrointestinal tractGastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
. Time to peak plasma concentration is 43 minutes and half-life is 11.6 hours. Unlike most other drugs, phenelzine irreversibly disables MAO, and as a result, 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 actually wear off until the body replenishes its enzyme stores, a process which can take as long as 2–3 weeks.
Phenelzine is metabolized primarily in the liver and its metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
s are excreted in the urine. Oxidation is the primary routine 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 the course of 96 hours after single doses. Acetylation to N2-acetylphenelzine is a minor pathway. Phenelzine may also interact with cytochrome P450 enzymes, inactivating these enzymes through formation of a heme adduct. Two other minor metabolites of phenelzine, as mentioned above, include phenylethylidenehydrazine and phenethylamine.
Chemistry
Phenelzine is made relatively easily through the reaction of 2-phenylethylbromide2-Phenylethylbromide
2-Phenylethylbromide is an organobromide that can be produced by the action of bromine and red phosphorus on 2-phenylethanol.It is moderately toxic by ingestion.When reacted with hydrazine, phenelzine is produced....
with hydrazine
Hydrazine
Hydrazine is an inorganic compound with the formula N2H4. It is a colourless flammable liquid with an ammonia-like odor. Hydrazine is highly toxic and dangerously unstable unless handled in solution. Approximately 260,000 tons are manufactured annually...
.
Adverse effects
Common side effects of phenelzine may include dizzinessDizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, blurry vision, dry mouth, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, lethargy, sedation
Sedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
, somnolence
Somnolence
Somnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
, insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, anorexia
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
, weight gain
Weight gain
Weight gain is an increase in body weight. This can be either an increase in muscle mass, fat deposits, or excess fluids such as water.-Description:...
or loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
, urinary retention
Urinary retention
Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
, mydriasis
Mydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...
, muscle tremors, hyperthermia
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...
, sweating
Sweating
Perspiration is the production of a fluid consisting primarily of water as well as various dissolved solids , that is excreted by the sweat glands in the skin of mammals...
, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
or hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, orthostatic hypotension
Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...
, paresthesia
Paresthesia
Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
, hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
, and sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
(consisting of loss of libido
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...
and anorgasmia
Anorgasmia
Anorgasmia, or Coughlan's syndrome, is a type of sexual dysfunction in which a person cannot achieve orgasm, even with adequate stimulation. In males the condition is often related to delayed ejaculation . Anorgasmia can often cause sexual frustration...
). Rare side effects usually only seen in susceptible individuals may include hypomania
Hypomania
Hypomania is a mood state characterized by persistent and pervasive elevated or irritable mood, as well as thoughts and behaviors that are consistent with such a mood state...
or mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...
, psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
, and acute liver failure, the latter of which is usually only seen in people with pre-existing liver damage, old age
Old age
Old age consists of ages nearing or surpassing the average life span of human beings, and thus the end of the human life cycle...
, alcohol consumption
Long-term effects of alcohol
The long term effects of alcohol range from possible health benefits for low levels of alcohol consumption to severe detrimental effects in cases of chronic alcohol abuse...
, or viral infection.
Interactions
The MAOIs are infamous for their problematic food restrictions and drug interactions. Hypertensive crisis may result from the overconsumption of tyramineTyramine
Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent...
-containing foods. As a result, patients on phenelzine and other MAOIs must avoid excess quantities of certain foods that contain tyramine such as aged cheeses and cured meats, among others. Serotonin syndrome
Serotonin syndrome
Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...
may result from an interaction with certain drugs which increase serotonin activity such as selective serotonin reuptake inhibitors and pethidine
Pethidine
Pethidine or meperidine Pethidine (INN) or meperidine (USAN) Pethidine (INN) or meperidine (USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Mialgin (in Indonesia); Petidin Dolargan (in Poland);...
(known as meperidine in the US). Several deaths have been reported due to drug interaction-related serotonin syndrome
Serotonin syndrome
Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...
such as the case of Libby Zion.
As is the case with other MAOIs there is a concern regarding Phenelzine and the use of anesthetics, both Local
Local anesthetic
A local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...
and General anesthetic
General
A general officer is an officer of high military rank, usually in the army, and in some nations, the air force. The term is widely used by many nations of the world, and when a country uses a different term, there is an equivalent title given....
. Anyone taking Phenelzine should inform their Psychiatrist before proceeding with dental surgery, and surgery in any other contexts. See the MAOI page for further information on this particular concern.
Phenelzine has also been linked to vitamin B6
Vitamin B6
Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
deficiency. It reacts with vitamin B6 via an unknown enzyme to form a biologically inert metabolite. Both phenelzine and vitamin B6 are rendered inactive upon this reaction occurring. For this reason, it is recommended to supplement with vitamin B6 while taking phenelzine. High doses of vitamin B6 may significantly lower phenelzine levels and subsequently inhibit its therapeutic benefits, however, and thus, excess quantities of vitamin B6 should be avoided. It may be advisable to dose them separately during opposite intervals of the day (e.g., take one, then take the other 12 hours later) to avoid interaction as much as possible.
See also
- Hydrazine (antidepressant)Hydrazine (antidepressant)The hydrazine antidepressants are a group of non-selective and irreversible monoamine oxidase inhibitors that were discovered and initially marketed in the 1950s and '60s...
- Monoamine oxidase inhibitorMonoamine oxidase inhibitorMonoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
- TranylcypromineTranylcypromineTranylcypromine is a drug of the substituted phenethylamine and amphetamine classes which acts as a monoamine oxidase inhibitor —it is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase...
- IsocarboxazidIsocarboxazidIsocarboxazid is an irreversible and nonselective monoamine oxidase inhibitor of the hydrazine chemical class used as an antidepressant and anxiolytic...