In a concentration-dependent manner, selegiline hydrochloride (1 nM-1 μM) inhibits recombinant human MAO-B[1]. Selegiline (10 mM) hydrochloride enhanced norepinephrine (NE), dopamine (DA), and serotonin (5-HT) efflux from the rat hypothalamus in vitro tests. In a dose-dependent manner, selegiline hydrochloride inhibits the efflux of 5-hydroxyindoleacetic acid (5-HIAA) and dihydroxyphenylacetic acid (DOPAC) [3].

In mice, selegiline hydrochloride (1 mg/kg; intraperitoneal injection daily for 24 days) decreased cocaine self-administration but had no effect on weight loss caused by cocaine. The concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the frontal cortex are lowered by selegiline hydrochloride [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
Selegiline and its metabolites are widely distributed throughout the body and can cross the blood-brain barrier. In mice, intravenous injection of radiolabeled selegiline hydrochloride resulted in rapid and widespread distribution of the parent drug and/or metabolites in the brain, liver, kidneys, lungs, heart, and brown adipose tissue. In healthy adults, intravenous injection of radiolabeled selegiline hydrochloride led to the most significant accumulation of radioactive material in the thalamus, basal ganglia, midbrain, and cingulate gyrus. /Selegiline/ Selegiline is primarily excreted in the urine as both bound and unbound metabolites. After oral administration, approximately 20-63% of selegiline is excreted in the urine as L-methamphetamine, 9-26% as L-amphetamine, and 1% as L-desmethylselegiline. Approximately 15% of the dose is excreted in the feces within 72 hours after administration. /SRP: Failure to identify the d/l-isomer in the sample often leads to false positive results in d-methamphetamine drug testing. /Selegiline/
It is rapidly absorbed from the gastrointestinal tract.
...The mean peak plasma concentration (Cmax) is approximately 2 μg/L, with a time to peak concentration of less than 1 hour. The absolute bioavailability of selegiline is approximately 10%. Its apparent volume of distribution is 1854 L. The oral clearance of selegiline (59 L/min) is significantly higher than the hepatic blood flow (1.5 L/min), indicating that extrahepatic pathways are involved in the clearance of selegiline. Selegiline is readily absorbed from the gastrointestinal tract after oral administration and rapidly enters the brain and spinal cord. The drug binds to brain regions with high MAO-B content, such as the thalamus, striatum, cortex, and brainstem. Selegiline is primarily excreted in the urine as bound and unbound metabolites. Following oral administration of selegiline, approximately 20-63% is excreted in the urine as L-methamphetamine, 9-26% as L-amphetamine, and 1% as L-desmethylselegiline. Selegiline is rapidly and completely metabolized to N-desmethyldeprazole, levometamethamine, and levometamethamine. Selegiline is extensively metabolized, presumably through cytochrome P450-mediated oxidation to levometamethamine and levometamethamine, the latter being further metabolized to levometamethamine. Selegiline is metabolized in the lungs to levometamethamine and levometamethamine, and in the kidneys to levometamethamine, but the degree of metabolism in these tissues is extremely low compared to the liver. The pharmacokinetics of selegiline are highly variable. After oral administration of 10 mg selegiline, it is rapidly absorbed and metabolized to desmethylselegiline, levometamethamine, and levometamethamine. /Selegiline/
For more complete metabolite/data on selegiline hydrochloride (6 metabolites), please visit the HSDB record page.

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Biological half-life
Elimination: Selegiline: 39 (range, 16 to 69) hours. /Selegiline/
The mean half-lives of the three active metabolites detected in serum and urine after a single dose of selegiline are as follows: N-desmethyldeprazole, 2 hours; levamisole, 17.7 hours; levamisole, 20.5 hours. /Selegiline/

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Clinical cases of selegiline use during lactation are extremely rare. Although there have been no reports of adverse reactions in breastfed infants, alternative medications are recommended, especially when breastfeeding 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 the medication after breastfeeding her infant for 3 days. The infant was followed up for 10 years and no developmental abnormalities were found.
A woman with severe depression used 6 mg of selegiline patch daily during pregnancy and postpartum. The duration of her exclusive breastfeeding was not specified. Pediatric follow-up at 5 months of age revealed normal infant development.
◉ Effects on Lactation and Breast Milk
Selegiline can reduce serum prolactin levels in women with migraines and women taking antipsychotic medications. The clinical significance of these findings for breastfeeding mothers is unclear. Prolactin levels in mothers who have established lactation may not affect their ability to breastfeed.

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Drug Interactions
While some patients appear to be sensitive to the vasopressor effects of sympathomimetic drugs during treatment with nonselective monoamine oxidase inhibitors, patients taking 10 mg or less of selegiline hydrochloride daily can generally take over-the-counter (OTC) or prescription cold or hay fever medications containing vasopressors (e.g., ephedrine, phenylpropanolamine) without increasing the risk of poor hypertension control. However, at least one patient reported a hypertensive crisis after receiving the recommended daily dose of 10 mg selegiline hydrochloride and a sympathomimetic drug (ephedrine).
In patients receiving levodopa, the addition of selegiline hydrochloride may exacerbate levodopa-related motor dysfunction. This side effect has an average incidence of 28% (range: 4-90%) in clinical trials, usually occurring within 2 weeks of starting selegiline treatment and typically lessening after reducing the levodopa dose… Patients taking levodopa and selegiline hydrochloride at doses exceeding 10 mg daily have experienced teeth grinding, muscle twitching, and myoclonus. Concomitant use of selegiline and tricyclic antidepressants has been associated with cardiac arrest, excessive sweating, hypertension, syncope, altered behavior and mental status, altered consciousness, high fever, seizures, muscle rigidity, and tremors. Concomitant use is not recommended; at least 14 days should be elapsed after discontinuing selegiline before starting tricyclic antidepressants. /Selegiline/ Rare reports indicate that concomitant use of selegiline and selective serotonin reuptake inhibitors (SSRIs) may result in serotonin syndrome-like reactions. (Serotonin syndrome may be caused by the co-administration of serotonergic drugs with monoamine oxidase inhibitors. This syndrome can manifest as altered mental status (confusion, hypomania), agitation, myoclonus, hyperreflexia, excessive sweating, chills, tremors, diarrhea, ataxia, and/or fever. If identified early, the syndrome usually resolves rapidly upon discontinuation of the causative drug.) Concomitant use of selegiline and selective serotonin reuptake inhibitors (SSRIs) is not recommended as it may lead to autonomic dysfunction, muscle rigidity, severe agitation, or delirium. At least 14 days should be elapsed after discontinuing a monoamine oxidase inhibitor before initiating SSRIs. However, due to the long half-life of fluoxetine and its active metabolites, at least 5 weeks (approximately 5 half-lives) should be elapsed after discontinuing fluoxetine before initiating monoamine oxidase inhibitor therapy. Furthermore, based on the half-life of venlafaxine, at least 7 days should be elapsed after discontinuing venlafaxine before initiating monoamine oxidase inhibitor (MAO inhibitor) therapy. /Selegiline/
For more complete data on interactions of selegiline hydrochloride (9 in total), please visit the HSDB record page.

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Non-human toxicity values
Subcutaneous LD50 in rats: 280 mg/kg
Intravenous LD50 in rats: 81 mg/kg

[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 hydrochloride is the hydrochloride form of selegiline, a levo-acetylene derivative belonging to the phenylethylamine class of compounds with anti-Parkinson's disease activity. As a selective monoamine oxidase (MAO) inhibitor, selegiline has the highest affinity for MAO type B, which is primarily found in the brain. Selegiline is converted to its active moiety via MAO type B, which irreversibly binds to the active site of the enzyme's cofactor FAD (flavin adenine dinucleotide) molecule. This inhibits the oxidative deamination of catecholamines and serotonin by MAO B, thereby enhancing the activity of these neurotransmitters and ultimately improving motor function. Furthermore, the drug may inhibit the reuptake of dopamine by neurons, thus prolonging dopamine activity. A selective, irreversible monoamine oxidase inhibitor used to treat newly diagnosed Parkinson's disease patients and depression. The compound without an isomer name is deprenyl. See also: Selegiline (with active moiety).

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Mechanism of Action
Selegiline's action is believed to be related to its irreversible inhibition of monoamine oxidase type B (MAO B), the predominant form of this enzyme in the human brain. MAO B is involved in the oxidative deamination of dopamine in the brain, and it is inhibited when selegiline covalently and stoichiometrically binds to isorhodin-adenine dinucleotide (FAD) at the active site of MAO B. A daily dose of 10 mg of selegiline almost completely inhibits MAO-B in the brain. At higher doses (potentially 20 to 40 mg daily), selegiline becomes a non-selective inhibitor of all monoamine oxidases (MAO). At these doses, a tyramine-mediated MAO-A blocking hypertensive response (“cheese reaction”) may occur. Selegiline (or its metabolites) may also enhance dopaminergic activity through other mechanisms, including interference with dopamine reuptake at synapses. The mechanism of action of selegiline is complex and cannot be explained solely by its MAO-B inhibitory effect. Selegiline pretreatment protects neurons from damage by various neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), methyl-β-acetoxyethyl-2-chloroethylamine (AF64A), and 5,6-dihydroxyserotonin. These toxins damage dopaminergic, adrenergic, cholinergic, and serotonergic neurons, respectively. Selegiline has amphetamine-like effect, enhancing dopamine release and blocking dopamine reuptake. It stimulates gene expression of L-aromatic amino acid decarboxylases, increases striatal phenylethylamine levels, and activates dopamine receptors. Selegiline reduces the production of oxidative free radicals, upregulates the activity of superoxide dismutase and catalase, and inhibits non-enzymatic and iron-catalyzed aoxidation of dopamine. Selegiline compensates for the lack of nutritional support from target cells, delays apoptosis in serum-deprived cells, and prevents apoptosis-related decline in mitochondrial membrane potential. Most of these properties are unrelated to selegiline's efficacy in inhibiting MAO-B. /Selegiline/
Selegiline is a selective monoamine oxidase B (MAO-B) inhibitor, administered at a daily dose of 10 mg, for patients with Parkinson's disease as adjunctive therapy to levodopa. By inhibiting MAO-B, selegiline increases dopamine levels in the substantia nigra. Selegiline also blocks the reuptake of dopamine in the synaptic cleft, thereby increasing dopamine concentration in the brain. ……/Selegiline/
For more complete data on the mechanisms of action of selegiline hydrochloride (one of six), please visit the HSDB record page.

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Therapeutic Use
Monoamine Oxidase B Inhibitor
Selegiline is indicated for use in combination with levodopa or levodopa in combination with carbidopa for the treatment of idiopathic Parkinson's disease (tremor). /US Product Label Contains//Selegiline/
…We briefly report on immunodeficiency virus-related neurotoxicity and discuss the effects of selegiline (a monoamine oxidase inhibitor that enhances dopamine availability in the central nervous system) on immunodeficiency virus-induced neurological disorders. …Monoamine oxidase inhibitors may be potent mediators of neuropathological defects in immunodeficiency virus infection and may also be factors that accelerate the progression of immunodeficiency virus-related neurological disorders.
EXPTL Therapy:…Twenty patients with mild to moderate pathological brain atrophy (atrophic and/or vascular) received selegiline (levodipril), a monoamine oxidase B inhibitor (10 mg/day for 6 months). Compared with the control group, patients in the selegiline treatment group showed statistically significant improvements in cognitive and behavioral abilities. At the end of the study, the Mini-Mental State Examination (MMSE) showed an improvement of 26.5% in the selegiline group, compared with only 3.7% in the control group (P < 0.01). The Clinical Intelligence Ability Scale (ECA) showed a 29.4% improvement in the selegiline group, compared to only a 10.8% improvement in the control group (P < 0.01). Selegiline treatment significantly reduced reaction time and improved memory. No side effects were observed during the study. /Selegiline/
For more complete data on the therapeutic uses of selegiline hydrochloride (of 10 types), please visit the HSDB record page.

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Drug Warnings
Pregnancy Risk Grade: C / Risk cannot be ruled out. Adequate, well-controlled human studies are lacking, and animal studies have not shown any risk to the fetus. There is a possibility of fetal harm if this drug is taken during pregnancy; however, the potential benefits may outweigh the potential risks. /
Selegiline may reduce or inhibit saliva production, leading to dental caries, periodontal disease, oral candidiasis, and discomfort.
Therapeutic use may cause increased tremor, bradykinesia, falls, symptoms of dystonia, movement disorders, hallucinations, confusion, sleep disturbances, headache, dry mouth, blurred vision, orthostatic hypotension, hypertension, loss of appetite, urinary retention, and hyperhidrosis. Hypomanic behavior may be caused by levoamphenicol (the levoamphenicol compound in selegiline) and its metabolites.
Adding selegiline hydrochloride to patients taking levodopa may exacerbate levodopa-related movement disorders. This side effect has an average incidence of 28% (range: 4-90%) in clinical trials, usually occurs within 2 weeks of starting selegiline treatment, and usually lessens after reducing the levodopa dose… Patients taking selegiline may experience involuntary movements, increased tremor, chorea, balance disorders, frozen gait, blepharospasm, increased bradykinesia, facial contortions, speech disturbances, leg heaviness, neck stiffness, tardive dyskinesia, signs of dystonia, shuffling gait, increased apraxia, and muscle spasms. Patients taking more than 10 mg of levodopa and selegiline hydrochloride daily have experienced bruxism, muscle twitching, and myoclonus. For more complete data on selegiline hydrochloride (12 total), please visit the HSDB records page.

C13H17N.HCL

223.74172

223.112

14611-52-0

Selegiline;14611-51-9

26758

White to off-white solid powder

0.954g/cm3

272.5ºC at 760mmHg

141-142ºC

108.4ºC

2.984

1

1

4

15

195

1

C[C@H](CC1=CC=CC=C1)N(C)CC#C.Cl

IYETZZCWLLUHIJ-UTONKHPSSA-N

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

(2R)-N-methyl-1-phenyl-N-prop-2-ynylpropan-2-amine;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

DMSO : ~100 mg/mL (~446.95 mM)
H2O : ≥ 33.33 mg/mL (~148.97 mM)

Solubility in Formulation 1: ≥ 5 mg/mL (22.35 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 5 mg/mL (22.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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