Blood pressure is raised with rel-Tranylcypromine (SKF 385; intravenous injection, 0.1 to 3.0 mg/kg; mongrel dogs, 5-10 kg). The dosage that is given determines how much and how long the medicine raises blood pressure. It is typically possible to obtain the animal's depressor response to rel-Tranylcypromine by repeatedly administering the drug[1].

Absorption, Distribution and Excretion
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/

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Metabolism / Metabolites
Hepatic.

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Biological Half-Life
1.5-3.2 hours in patients with normal renal and hepatic function

Hepatotoxicity
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.
Likelihood score: D (possible rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because little information is available on the use of tranylcypromine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
A woman with severe depression took tranylcypromine 100 to 120 mg daily, as well as pimozide, diazepam and alprazolam during pregnancy and postpartum. She breastfed her infant until about 2 weeks postpartum when the infant developed abdominal distension and feeding intolerance. The symptoms resolved on discontinuation of breastfeeding.
◉ Effects on Lactation and Breastmilk
Nine subjects were treated with an average dose of 29 mg daily (range 10 to 40 mg daily) of oral tranylcypromine for an average of 16 days. Serum prolactin levels increased by 3 mcg/L.The clinical relevance of these findings in nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Interactions
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.

[1]. TODA N, et al. The sympathomimetic effects of SKF-385 on blood pressure in dog. Jpn J Pharmacol. 1962;12:166-179.

(1R,2S)-tranylcypromine is a 2-phenylcyclopropan-1-amine that is the (1R,2S)-enantiomer of tranylcypromine. It is a conjugate base of a (1R,2S)-tranylcypromine(1+). It is an enantiomer of a (1S,2R)-tranylcypromine.
A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders (From AMA Drug Evaluations Annual, 1994, p311). Tranylcypromine is a racemate comprising equal amounts of (1R,2S)- and (1S,2R)-2-phenylcyclopropan-1-amine with the chiral centers both located on the cylopropane ring. An irreversible monoamine oxidase inhibitor that is used as an antidepressant (INN tranylcypromine).
Tranylcypromine is a Monoamine Oxidase Inhibitor. The mechanism of action of tranylcypromine is as a Monoamine Oxidase Inhibitor.
Tranylcypromine is a nonhydrazine monoamine oxidase inhibitor (MAO inhibitor) used in therapy of severe depression. Tranylcypromine therapy is associated with rare instances of clinically apparent acute liver injury.
Tranylcypromine is an orally bioavailable, nonselective, irreversible, non-hydrazine inhibitor of both monoamine oxidase (MAO) and lysine-specific demethylase 1 (LSD1/BHC110), with antidepressant and anxiolytic activities, and potential antineoplastic activities. Upon oral administration, tranylcypromine exerts its antidepressant and anxiolytic effects through the inhibition of MAO, an enzyme that catalyzes the breakdown of the monoamine neurotransmitters serotonin, norepinephrine, epinephrine and dopamine. This increases the concentrations and activity of these neurotransmitters. Tranylcypromine exerts its antineoplastic effect through the inhibition of LSD1. Inhibition of LSD1 prevents the transcription of LSD1 target genes. LSD1, a flavin-dependent monoamine oxidoreductase and a histone demethylase, is upregulated in a variety of cancers and plays a key role in tumor cell proliferation, migration, and invasion.
A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311)
See also: Tranylcypromine Sulfate (has salt form).

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Drug Indication
For the treatment of major depressive episode without melancholia.

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Mechanism of Action
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.

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Therapeutic Uses
Antidepressive Agents; Monoamine Oxidase Inhibitors; Anti-Anxiety Agents
DEG TO WHICH MAO IS INHIBITED IN PARTICULAR ORGAN OF BODY VARIES WITH PARTICULAR MAO INHIBITOR. SINCE MAO INHIBITION CANNOT BE EASILY MONITORED IN CLINICAL SITUATIONS (BECAUSE OF LONG LATENCY & DURATION OF ACTION), DRUGS ARE NEVER ADMIN PARENTERALLY. /MAO INHIBITORS/
MOST USEFUL EFFECT OF VARIOUS MAO INHIBITORS IS TO ELEVATE MOOD OF DEPRESSED PT. /MAO INHIBITORS/
MAO INHIBITORS ARE AMONG MOST EFFECTIVE REM SUPPRESSORS KNOWN. THIS EFFECT HAS BEEN USED THERAPEUTICALLY IN TREATMENT OF NARCOLEPSY. ... MAO INHIBITORS LOWER BLOOD PRESSURE & PROVIDE SYMPTOMATIC RELIEF IN ANGINA PECTORIS. /MAO INHIBITORS/
For more Therapeutic Uses (Complete) data for TRANYLCYPROMINE (11 total), please visit the HSDB record page.

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Drug Warnings
MAJORITY OF SMALL NUMBER OF DEATHS...OCCURRED AFTER DOSES OF OVER 350 MG; PT HAVE SURVIVED AFTER INGESTION OF THIS AMT, HOWEVER. DEPENDENCE ON TRANYLCYPROMINE HAS BEEN REPORTED OCCASIONALLY. /SULFATE/
...CONTRAINDICATED IN PT WITH CEREBROVASCULAR DEFECTS, CARDIOVASCULAR DISORDERS OR PHEOCHROMOCYTOMA... /SULFATE/
SWITCHING PT FROM ONE MAO INHIBITOR TO ANOTHER OR TO TRICYCLIC ANTIDEPRESSANT REQUIRES REST PERIOD OF 10-14 DAYS. /MAO INHIBITORS/
...TRANYLCYPROMINE CAN CAUSE REACTION IF ADMIN WHEN EFFECT OF PHENELZINE IS STILL PRESENT.
For more Drug Warnings (Complete) data for TRANYLCYPROMINE (20 total), please visit the HSDB record page.

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Pharmacodynamics
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.

C9H11N

133.19

133.089

155-09-9

Tranylcypromine hemisulfate;13492-01-8;Tranylcypromine-d5 hydrochloride;107077-98-5

19493

Liquid

1.1±0.1 g/cm3

218.3±29.0 °C at 760 mmHg

79-80 °C at 1.50E+00 mm Hg
MP: 164-166 °C /Hydrochloride/

90.8±19.6 °C

0.1±0.4 mmHg at 25°C

1.584

1.25

1

1

1

10

116

2

C1C=CC(C2C[C@H]2N)=CC=1

AELCINSCMGFISI-DTWKUNHWSA-N

InChI=1S/C9H11N/c10-9-6-8(9)7-4-2-1-3-5-7/h1-5,8-9H,6,10H2/t8-,9+/m0/s1

(1R,2S)-2-phenylcyclopropan-1-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)