Tranylcypromine

log Kow= 1.58 @ 25 °C

1.49

Sol in water /Sulfate/

Very slightly sol in alcohol, ether /Sulfate/

Practically insol in chloroform /Sulfate/

79-80 °C at 1.50E+00 mm Hg

MP: 164-166 °C /Hydrochloride/

EITHER ODORLESS OR HAS FAINT, CINNAMALDEHYDE-LIKE ODOR & SLIGHTLY ACID TASTE /SULFATE/

MELTS WITH DECOMP @ 218 °C /SULFATE/

Crystals /Sulfate/

Crystals from ethyl acetate & ether /Hydrochloride/

WHITE CRYSTALLINE POWDER /SULFATE/

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P264+P265, P270, P280, P301+P317, P302+P352, P305+P351+P338, P321, P330, P332+P317, P337+P317, P362+P364, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Treatment should normally consist of general supportive measures, close observation of vital signs and steps to counteract specific symptoms as they occur, since MAO inhibition may persist. External cooling is recommended if hyperpyrexia occurs. Barbiturates have been reported to help relieve myoclonic reactions, but frequency of administration should be controlled carefully because Tranylcypromine may prolong barbiturate activity. When hypotension requires treatment, the standard measures for managing circulatory shock should be initiated. If pressor agents are used, the rate of infusion should be regulated by careful observation of the patient because an exaggerated pressor response sometimes occurs in the presence of MAO inhibition. (L1712)

HEXOBARBITAL SLEEPING TIME IS PROLONGED BY PARNATE, INDICATING ITS ABILITY TO POTENTIATE OTHER DRUGS PRESUMABLY BY INTERFERING WITH THEIR DETOXIFICATION. /PARNATE/

MAO INHIBITORS ALSO ENHANCE EFFECTS OF EXOGENOUSLY ADMIN AMINES, SUCH AS 5-HT & NOREPINEPHRINE, AS WELL AS PRECURSORS, SUCH AS 3,4-HYDROXYPHENYLALANINE (DOPA) & 5-HYDROXYTRYPTOPHAN. /MAO INHIBITORS/

Meperidine should never be used for ... headaches /with the hypertensive episode/, and blood pressure should be evaluated immediately when a patient taking an MAO inhibitor reports a severe throbbing headache or a feeling of pressure in the head. /MAO INHIBITORS/

MAO INHIBITORS ... INTERFERE WITH DETOXICATION MECHANISMS FOR CERTAIN OTHER DRUGS. THEY PROLONG & INTENSIFY EFFECTS OF CENTRAL DEPRESSANT AGENTS, SUCH AS GENERAL ANESTHETICS, SEDATIVES, ANTIHISTAMINES, ALCOHOL, & POTENT ANALGESICS; OF ANTICHOLINERGIC AGENTS, PARTICULARLY THOSE USED IN THE TREATMENT OF PARKINSONISM; & OF ANTIDEPRESSANT AGENTS, ESP IMIPRAMINE & AMITRIPTYLINE. /MAO INHIBITORS/

For more Interactions (Complete) data for TRANYLCYPROMINE (37 total), please visit the HSDB record page.

Rare cases have been reported of hypertensive crisis, serotonin syndrome, myoclonus, hyperpyrexia, psychosis, and delirium, some of which progressed to coma. Additionally, in sensitive individuals or at extreme dosages, hypotension may lead to shock. [Wikipedia]

Tranylcypromine, like most monoamine oxidase inhibitors, can cause transient serum aminotransferase elevations in a proportion of patients. These elevations are usually mild, asymptomatic and self-limited and do not require dose modification. Tranylcypromine has also been associated with rare cases of acute, clinically apparent liver injury. The few cases described have resembled those caused by other MAO inhibitors. The time to clinical onset is typically 1 to 4 months and the usual pattern of serum enzyme elevations is hepatocellular (Case 1), although cholestatic injury has also been described. Immunoallergic features (rash, fever, eosinophilia) are uncommon as is autoantibody formation.

Common adverse effects of tranylcypromine include dry mouth, headaches, diarrhea, urinary hesitancy, insomnia, agitation, anxiety, nausea, and sexual dysfunction. Postural hypotension, sometimes leading to syncope, is another common adverse effect that warrants special attention for older patients on this medication. This adverse effect is dose-related and may require splitting the dose into 3 to 4 doses daily. More serious side effects include hepatotoxicity, seizures, and induction of mania. Additionally, in the United States, there is a black-box warning stating that this medication may lead to the activation of suicidal ideation and behavior in children, adolescents, and young adults aged 18 to 24 with major depressive disorder and other psychiatric disorders.

Interindividual variability in absorption. May be biphasic in some individuals. Peak plasma concentrations occur in one hour following oral administration with a secondary peak occurring within 2-3 hours. Biphasic absorption may represent different rates of absorption of the stereoisomers of the drug, though additional studies are required to confirm this.

Signs and Symptoms of Overdose

Tranylcypromine irreversibly and nonselectively inhibits monoamine oxidase (MAO). Within neurons, MAO appears to regulate the levels of monoamines released upon synaptic firing. Since depression is associated with low levels of monoamines, the inhibition of MAO serves to ease depressive symptoms, as this results in an increase in the concentrations of these amines within the CNS.

In overdosage, some patients exhibit insomnia, restlessness and anxiety, progressing in severe cases to agitation, mental confusion and incoherence. Hypotension, dizziness, weakness and drowsiness may occur, progressing in severe cases to extreme dizziness and shock. A few patients have displayed hypertension with severe headache and other symptoms. Rare instances have been reported in which hypertension was accompanied by twitching or myoclonic fibrillation of skeletal muscles with hyperpyrexia, sometimes progressing to generalized rigidity and coma.

EFFECTS OF OVERDOSAGE INCL AGITATION, HALLUCINATIONS, HYPERREFLEXIA, HYPERPYREXIA, & CONVULSIONS. BOTH HYPOTENSION & HYPERTENSION ALSO OCCUR. /MAO INHIBITORS/

CHRONIC TOXICITY. ... MOST DANGEROUS ARE THOSE INVOLVING LIVER, BRAIN, & CARDIOVASCULAR SYSTEM. ... HYPERSENSITIVITY MAY BE RESPONSIBLE MECHANISM... /MAO INHIBITORS/

...HAS EXHIBITED NO SPECIFIC OR SELECTIVE OCULAR TOXIC EFFECT IN USUAL DOSAGE OF 20 MG/DAY, BUT LARGE OVERDOSAGE TAKEN WITH SUICIDAL INTENT APPEARS TO HAVE RESULTED IN OCULAR & VISUAL DISTURBANCES IN 2 CASES.

66-YR-OLD MAN TREATED FOR DEPRESSION (TRANYLCYPROMINE SULFATE 10 MG 3 TIMES/DAY FOR 6 DAYS) DEVELOPED INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION WHICH DISAPPEARED AFTER DISCONTINUATION.

For more Human Toxicity Excerpts (Complete) data for TRANYLCYPROMINE (8 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

tranylcypromine

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

IN ANIMALS IT PRODUCES IRRITABILITY, RESTLESSNESS, HYPERREFLEXIA, HYPERTONIA, SALIVATION, LACRIMATION, MYDRIASIS, & MILD ELEVATIONS IN BLOOD PRESSURE. IT SUPPRESSES APPETITE...

TRANYLCYPROMINE 20 MG/KG PARENTERAL TO RATS INCR BRAIN SEROTONIN CONCN & DECR BRAIN GLYCOGEN; NO EFFECT ON BRAIN PHOSPHORYLASE A & B ACTIVITIES OR ON BRAIN ABILITY TO PRODUCE LACTATE ANAEROBICALLY FROM GLYCOGEN (THESE CONSIDERED INDICATORS OF GLYCOGENOLYSIS).

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

N - Nervous system

QN - Nervous system

Tranylcypromine belongs to a class of antidepressants called monoamine oxidase inhibitors (MAOIs). Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor with a rapid onset of activity. MAO is an enzyme that catalyzes the oxidative deamination of a number of amines, including serotonin, norepinephrine, epinephrine, and dopamine. Two isoforms of MAO, A and B, are found in the body. MAO-A is mainly found within cells located in the periphery and catalyzes the breakdown of serotonin, norepinephrine, epinephrine, dopamine and tyramine. MAO-B acts on phenylethylamine, norepinephrine, epinephrine, dopamine and tyramine, is localized extracellularly and is found predominantly in the brain. While the mechanism of MAOIs is still unclear, it is thought that they act by increasing free serotonin and norepinephrine concentrations and/or by altering the concentrations of other amines in the CNS. It has been postulated that depression is caused by low levels of serotonin and/or norepinephrine and that increasing serotonergic and norepinephrinergic neurotransmission results in relief of depressive symptoms. MAO A inhibition is thought to be more relevant to antidepressant activity than MAO B inhibition. Selective MAO B inhibitors, such as selegiline, have no antidepressant effects.

Tranylcypromine irreversibly and nonselectively inhibits monoamine oxidase (MAO). Within neurons, MAO appears to regulate the levels of monoamines released upon synaptic firing. Since depression is associated with low levels of monoamines, the inhibition of MAO serves to ease depressive symptoms, as this results in an increase in the concentrations of these amines within the CNS.

RESULTS SUGGEST THAT D- & DL-TRANYLCYPROMINE HAVE DIRECT & INDIRECT ACTIONS ON TRYPTAMINERGIC NEUROTRANSMISSION.

TRANYLCYPROMINE-HCL ADMIN IP (20 MG/KG) TO RATS: INCR IN HIPPOCAMPUS & DIENCEPHALON CONCN OF 2-PHENYLETHYLAMINE & TRYPTAMINE WERE MUCH HIGHER THAN THOSE OF M- & P-TYRAMINE. THESE MAY BE INVOLVED IN CNS NEURONAL FUNCTIONING, THEREFORE COMPONENT OF TRANYLCYPROMINE ACTIVITY.

PLATELET MAO ACTIVITY MARKEDLY DECR (DL-TRANYLCYPROMINE SULFATE 10 & 20 MG ORAL): UPTAKE OF 5-HYDROXYTRYPTAMINE, DOPAMINE & METARAMINOL ONLY SLIGHTLY DECR. MAO INHIBITOR ANTIDEPRESSANT ACTIVITY PROBABLY LESS RELATED TO CATECHOLAMINE UPTAKE INHIBITION THAN OXIDASE INHIBITION

...PRODUCE IRREVERSIBLE INACTIVATION OF MAO BY FORMING STABLE COMPLEXES WITH ENZYME. ... THERE IS EVIDENCE THAT SOME MAO INHIBITORS PREVENT RELEASE OF NOREPINEPHRINE FROM NERVE ENDINGS BY NERVE IMPULSES. /MAO INHIBITORS/

... TRANYLCYPROMINE IS A POTENT BUT NOT SPECIFIC INHIBITOR OF CYP2C19.

Hepatic.

Hepatic. Half Life: 1.5-3.2 hours in patients with normal renal and hepatic function

3E3V44J4Z9

TRANYLCYPROMINE

Established Pharmacologic Class [EPC] - Monoamine Oxidase Inhibitor

Mechanisms of Action [MoA] - Monoamine Oxidase Inhibitors

Tranylcypromine is a Monoamine Oxidase Inhibitor. The mechanism of action of tranylcypromine is as a Monoamine Oxidase Inhibitor.

TRANYLCYPROMINE

Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.

A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414)

Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.

Interindividual variability in absorption. May be biphasic in some individuals. Peak plasma concentrations occur in one hour following oral administration with a secondary peak occurring within 2-3 hours. Biphasic absorption may represent different rates of absorption of the stereoisomers of the drug, though additional studies are required to confirm this.

1.1-5.7 L/kg

THE MAO INHIBITORS ARE ABSORBED READILY WHEN GIVEN BY MOUTH. THESE DRUGS PRODUCE MAXIMAL INHIBITION OF MAO WITHIN 5-10 DAYS. ... ALTHOUGH THEIR BIOLOGICAL ACTIVITY IS PROLONGED BECAUSE OF THE CHARACTERISTICS OF THEIR INTERACTION WITH THE ENZYME, THEIR CLINICAL EFFICACY APPEARS TO BE REDUCED WHEN THE DRUG IS GIVEN LESS FREQUENTLY THAN ONCE DAILY. /MAO INHIBITORS/

MEDICATION

Use (kg; approx.) in Germany (2009): >25

Primarily indicated for the treatment of clinical depression. It is generally used to remedy various types of mood and anxiety disorders, typically after a last resort only after conventional antidepressants have been tried without success. It also has some off-label uses, such as in the treatment of post-traumatic stress disorder (PTSD). [Wikipedia]

Parnate, Tylciprine /Sulfate/

DOSAGE FORMS--TABLETS NF: 10 MG. /SULFATE/