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 from the gastrointestinal tract.

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Metabolism / Metabolites
Selegiline has known human metabolites that include Desmethylselegiline and Methamphetamine.

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Biological Half-Life
1.2-2 hours

Hepatotoxicity
Selegiline has been reported to cause serum enzyme elevations in up to 40% of patients treated long term. Although the abnormalities were usually mild and self-limiting, they were persistent with continuation of treatment in some patients, ultimately requiring drug discointuation. Selegiline has not been implicated in cases of clinically apparent acute liver injury, but such instances have been reported with other less specific MAO inhibitors.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
A minimal amount of clinical use of selegiline during breastfeeding has been reported. Although no adverse reactions have been reported in the breastfed infants, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. The manufacturer of the selegiline transdermal patch recommends that breastfeeding is not recommended during treatment and for 7 days after the final dose.
◉ Effects in Breastfed Infants
A woman took selegiline 10 mg, levodopa 400 mg and benserazide 100 mg daily throughout pregnancy and continued them while breastfeeding her infant for 3 days. The child was followed for 10 years and no developmental abnormalities were found.
A woman with severe depression used a selegiline patch 6 mg per day during pregnancy and postpartum. She exclusively breastfed her infant for an unstated period of time. Pediatric follow-up at 5 months of age found that the infant was developing normally.
◉ Effects on Lactation and Breastmilk
Selegiline can decrease serum prolactin in women with migraine, and in those taking neuroleptic drugs. 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.
◈ What is selegiline?
Selegiline is a medication approved to treat major depressive disorder and to help treat Parkinson’s disease. It has also been used to treat other medical conditions. It is in a class of medications known as selective inhibitors of monoamine oxidase type B. It is available as a skin (transdermal) patch, sold under the name Emsam®. It can also be taken by mouth (orally) and is sold under brand names such as Eldepryl® and Zelapar®.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. In general, monoamine oxidase inhibitors are avoided during pregnancy because of their side effects and interactions with other medications. However, they have been used when other medications have not been effective. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.If you and your healthcare provider decide that you should stop this medication, you should discuss the best way to stop. It may be suggested to slowly lower the amount taken (taper off) because some people can experience withdrawal symptoms after stopping monoamine oxidase inhibitors. This may include flu-like symptoms such as sweating, chills, nausea, and headaches, as well as anxiety, agitation, and trouble sleeping.If you are taking this medication for depression, MotherToBaby has a fact sheet on depression at: https://mothertobaby.org/fact-sheets/depression-pregnancy/.
◈ I take selegiline. Can it make it harder for me to get pregnant?
Answer if info available; otherwise: It is not known if selegiline can make it harder to get pregnant.
◈ Does taking selegiline increase the chance of miscarriage?
Miscarriage is common and can occur in any pregnancy for many different reasons. Studies have not been done to see if selegiline could increase the chance for miscarriage.
◈ Does taking selegiline increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. It is not known if taking selegiline could increase the chance for birth defects. Experimental animal studies did not find a higher chance for birth defects. There are 3 case reports on people who became pregnant while being treated with selegiline and other medications. Two people stopped taking selegiline and 1 continued to use the medication through the pregnancy; all 3 had healthy infants.
◈ Does taking selegiline in pregnancy increase the chance of other pregnancy related problems?
Studies have not been done to see if selegiline increases the chance for pregnancy-related problems such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth).
◈ Does taking selegiline in pregnancy affect future behavior or learning for the child?
Studies have not been done to see if selegiline can cause behavior or learning issues for the child.
◈ Breastfeeding while taking selegiline:
Selegiline has not been well studied for use while breastfeeding. There are 2 case reports of breastfeeding; no reported issues with development was reported. It is not known how much selegiline would get into breastmilk. Be sure to talk to your healthcare provider about all of your breastfeeding questions.
◈ If a male takes selegiline, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Studies have not been done to see if selegiline could affect male fertility or increase the chance of birth defects. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures 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 and a terminal acetylenic compound. It has a role as a geroprotector. It is a conjugate base of a (-)-selegiline(1+).
A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl.
Selegiline is a Monoamine Oxidase Inhibitor and Monoamine Oxidase Type B Inhibitor. The mechanism of action of selegiline is as a Monoamine Oxidase Inhibitor and Monoamine Oxidase-B Inhibitor.
Selegiline is an inhibitor of monamine oxidase used in the treatment of depression and as adjunctive therapy in combination with levodopa and carbidopa in the therapy of Parkinson disease. Selegiline has been associated with a low rate of serum enzyme elevations during treatment, but has not been linked to instances of clinically apparent acute liver injury.
A selective, irreversible inhibitor of Type B monoamine oxidase that is used for the treatment of newly diagnosed patients with PARKINSON DISEASE, and for the treatment of depressive disorders. The compound without isomeric designation is Deprenyl.
See also: Selegiline Hydrochloride (has salt form).

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Drug Indication
Monotherapy for initial treatment of Parkinson's disease, as well as an adjunct therapy in patients with a decreased response to levodopa/carbadopa. Also used for the palliative treatment of mild to moderate Alzheimer's disease and at higher doses, for the treatment of depression.
FDA Label

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Mechanism of Action
Although the mechanisms for selegiline's beneficial action in the treatment of Parkinson's disease are not fully understood, the selective, irreversible inhibition of monoamine oxidase type B (MAO-B) is thought to be of primary importance. MAO-B is involved in the oxidative deamination of dopamine in the brain. Selegiline binds to MAO-B within the nigrostriatal pathways in the central nervous system, thus blocking microsomal metabolism of dopamine and enhancing the dopaminergic activity in the substantial nigra. Selegiline may also increase dopaminergic activity through mechanisms other than inhibition of MAO-B. At higher doses, selegiline can also inhibit monozmine oxidase type A (MAO-A), allowing it to be used for the treatment of depression.

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Pharmacodynamics
Dopamine is an essential chemical that occurs in many parts of the body. It is the premature degradation of dopamine that results in the symptoms of Parkinson's disease. Monoamine oxidase (MAO) is an enzyme which accelerates the breakdown of dopamine. Selegiline can prolong the effects of dopamine in the brain by preventing its breakdown through seletively blocking MAO-B. It also may prevent the removal of dopamine between nerve endings and enhance 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.)