Recombinant human MAO-B is inhibited by selegiline (1 nM-1 μM) in a concentration-dependent manner [1]. Selegiline (10 mM) increases the rat hypothalamus's efflux of norepinephrine (NE), dopamine (DA), and serotonin (5-HT). In a dose-dependent manner, selegiline inhibits the efflux of 5-hydroxyindoleacetic acid (5-HIAA) and dihydroxyphenylacetic acid (DOPAC) [3].

In mice, selegiline (1 mg/kg; intraperitoneal injection daily for 24 days) decreased cocaine self-administration but had no effect on weight loss caused by cocaine. In the frontal cortex, selegiline lowers the amounts of 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) [4].

Animal/Disease Models: Male C57BL/6J mice (20-22 g) [4]
Doses: 1 mg/kg
Route of Administration: daily intraperitoneal (ip) injection for 24 days
Experimental Results: A single injection does not seriously affect the locomotor activities of mice . Dosing for 14 days did not affect food reward. diminished cocaine self-administration and diminished DOPAC and 5-HIAA concentrations in the frontal cortex.

Absorption, Distribution and Excretion
Rapidly absorbed via the gastrointestinal tract. Metabolisms/Metabolites Known metabolites of selegiline include desmethylselegiline and methamphetamine. Biological Half-Life 1.2–2 hours

Hepatotoxicity
Up to 40% of patients taking selegiline long-term have reported elevated serum enzymes. While these abnormalities are usually mild and resolve spontaneously, they persist in some patients with continued treatment, eventually requiring discontinuation. Selegiline has not been reported to be associated with clinically significant acute liver injury, but such cases have been reported with other less specific monoamine oxidase inhibitors. Probability Score: E (Unlikely to cause clinically significant liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Selegiline has been reported to be used very rarely during lactation. While there have been no reports of adverse reactions in breastfed infants, alternative medications are recommended, especially for breastfed newborns or premature infants. The manufacturer of the selegiline transdermal patch recommends against breastfeeding during treatment and for 7 days after the last dose.
◉ Effects on Breastfed Infants
A woman took 10 mg of selegiline, 400 mg of levodopa, and 100 mg of benserazide daily throughout her pregnancy and continued taking them for 3 days while breastfeeding her infant. The infant was followed up for 10 years and no developmental abnormalities were found.
A woman with major depressive disorder used a 6 mg selegiline patch daily during pregnancy and postpartum. The duration of her exclusive breastfeeding was not specified. A pediatric follow-up at 5 months of age found that the infant was developing normally.
◉ Effects on Lactation and Breast Milk
Selegiline can lower serum prolactin levels in women with migraines and women taking antipsychotic medications. The clinical significance of these findings for breastfeeding women is unclear. For mothers who have established lactation, prolactin levels may not affect their ability to breastfeed.
◈ What is Selegiline?
Selegiline is a drug approved for the treatment of major depressive disorder and as adjunctive therapy for Parkinson's disease. It has also been used to treat other conditions. It belongs to a class of drugs called selective monoamine oxidase type B inhibitors. It is sold as a transdermal patch under the brand name Emsam®. It can also be taken orally under the brand names Eldepryl® and Zelapar®. Sometimes, when people find out they are pregnant, they consider changing how they take the medication or even stopping it completely. However, it is essential to consult your healthcare provider before changing your medication. Generally, these medications should be avoided during pregnancy due to the side effects of monoamine oxidase inhibitors and their interactions with other medications. However, they can be used when other medications are ineffective. Your healthcare provider can discuss with you the benefits of treating your condition and the risks of not treating the condition during pregnancy. If you and your healthcare provider decide to stop taking this medication, you should discuss the best way to discontinue it. A gradual reduction in dosage (gradual tapering) is recommended because some people experience withdrawal symptoms after stopping monoamine oxidase inhibitors. These symptoms may include flu-like symptoms such as sweating, chills, nausea, and headache, as well as anxiety, irritability, and difficulty sleeping. If you are taking this medication to treat depression, MotherToBaby provides a fact sheet on depression at: https://mothertobaby.org/fact-sheets/depression-pregnancy/.
◈ I am taking selegiline. Will it make it harder for me to get pregnant?
Answer if relevant; otherwise: It is unclear whether selegiline increases the difficulty of conception.
◈ Does taking selegiline increase the risk of miscarriage?
Miscarriage is common and can occur in any pregnancy for a variety of reasons. There are currently no studies exploring whether selegiline increases the risk of miscarriage.
◈ Does taking selegiline increase the risk of birth defects?
There is a 3-5% risk of birth defects in every pregnancy, known as background risk. It is unclear whether taking selegiline increases the risk of birth defects. Animal studies have not found an increased risk of birth defects. There are 3 case reports of patients becoming pregnant while taking selegiline and other medications. Two patients discontinued selegiline, while one continued taking the medication throughout the pregnancy; all three women gave birth to healthy babies.
◈ Does taking selegiline during pregnancy increase the risk of other pregnancy-related problems?
There are currently no studies showing that selegiline increases the risk of preterm birth (delivery before 37 weeks of gestation) or low birth weight (birth weight less than 5 pounds 8 ounces [2500 grams]).
◈ Will taking selegiline during pregnancy affect a child's future behavior or learning?
There are currently no studies showing that selegiline causes behavioral or learning problems in children.
◈ Breastfeeding while taking selegiline:
There are currently no studies on the use of selegiline during breastfeeding. There are two case reports of breastfeeding patients taking selegiline; no developmental problems have been reported. It is currently unclear how much selegiline enters breast milk. Please consult your healthcare provider about all breastfeeding-related questions.
◈ If a man takes selegiline, will it affect his fertility (the ability to impregnate his partner) or increase the risk of birth defects?
Currently, no studies have explored whether selegiline affects male fertility or increases the risk of birth defects. Generally, exposure to this medication by the father or sperm donor is unlikely to increase the risk of pregnancy. For more information, please refer to the "Father's Exposure to Medications" information sheet on the MotherToBaby website at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

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Protein binding
> 99.5%

[1]. Selective Inhibition of Human Monoamine Oxidase B by Acacetin 7-Methyl Ether Isolated from Turnera diffusa (Damiana). Molecules. 2019 Feb 23;24(4):810.

[2]. Modulation of gene expression rather than monoamine oxidase inhibition: (-)-deprenyl-related compounds in controlling neurodegeneration. Neurology. 1996 Dec;47(6 Suppl 3):S171-83.

[3]. Deprenyl stimulates the efflux of monoamines from the rat hypothalamus in vitro. Brain Res Bull. 2001 Apr;54(6):675-80.

[4]. Chronic treatment with monoamine oxidase-B inhibitors decreases cocaine reward in mice. Psychopharmacology (Berl). 2009 Jul;205(1):141-9.

(-)-Selegiline is a selegiline-like compound and a terminal alkyne compound. It has anti-aging effects. It is the conjugate base of (-)-selegiline (1+). It is a selective, irreversible monoamine oxidase type B inhibitor. It is used in newly diagnosed Parkinson's disease patients. It can slow the progression of clinical disease and delay the need for levodopa treatment. It can also be used in combination with levodopa in cases of disability. (From JAMA Drug Evaluation Yearbook, 1994, p. 385) The compound whose isomer is not specified is selegiline (Deprenyl). Selegiline is a monoamine oxidase inhibitor, specifically a monoamine oxidase type B inhibitor. The mechanism of action of selegiline is as a monoamine oxidase inhibitor and a monoamine oxidase-B inhibitor. Selegiline is a monoamine oxidase inhibitor used to treat depression and can also be used in combination with levodopa and carbidopa as adjunctive therapy for Parkinson's disease. The incidence of elevated serum enzymes during selegiline treatment is low, but no clinically significant cases of acute liver injury have been observed. It is a selective, irreversible monoamine oxidase type B inhibitor used to treat newly diagnosed Parkinson's disease and depression. The compound for which no isomer is identified is deprenyl. See also: selegiline hydrochloride (salt form). Indications: As monotherapy for initial treatment of Parkinson's disease, and as adjunctive therapy in patients with reduced levodopa/carbadopa response. Also used for palliative care of mild to moderate Alzheimer's disease, and at high doses for the treatment of depression. FDA Label: Mechanism of Action: While the beneficial mechanism of action of selegiline in treating Parkinson's disease is not fully elucidated, selective and irreversible inhibition of monoamine oxidase type B (MAO-B) is considered the primary mechanism of action. MAO-B is involved in the oxidative deamination of dopamine in the brain. Selegiline binds to MAO-B in the substantia nigra-striatal pathway of the central nervous system, thereby blocking the metabolism of dopamine by microsomes and enhancing dopaminergic activity in the substantia nigra. Selegiline may also enhance dopaminergic activity through other mechanisms besides inhibiting MAO-B. At high doses, selegiline can also inhibit monoamine oxidase type A (MAO-A), making it potentially useful for treating depression.

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Pharmacodynamics
Dopamine is an essential chemical present in many parts of the body. Premature degradation of dopamine can lead to symptoms of Parkinson's disease. Monoamine oxidase (MAO) is an enzyme that accelerates the breakdown of dopamine. Selegiline can prevent the breakdown of dopamine by selectively blocking MAO-B, thereby prolonging the effects of dopamine in the brain. It can also prevent the clearance of dopamine between nerve endings and enhance the release of dopamine from nerve cells.

C13H17N

187.28078

187.136

14611-51-9

Selegiline hydrochloride;14611-52-0

26757

Typically exists as solid at room temperature

0.954g/cm3

272.5ºC at 760 mmHg

141-142 °C

108.4ºC

0.00606mmHg at 25°C

1.528

2.182

0

1

4

14

195

1

C#CCN(C)[C@H](C)CC1=CC=CC=C1

MEZLKOACVSPNER-GFCCVEGCSA-N

InChI=1S/C13H17N/c1-4-10-14(3)12(2)11-13-8-6-5-7-9-13/h1,5-9,12H,10-11H2,2-3H3/t12-/m1/s1

(2R)-N-methyl-1-phenyl-N-prop-2-ynylpropan-2-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.)