Selegiline hydrochloride

223.74

223.112778

2017-001-1

6W731X367Q

DTXSID9044584

C47714

Crystals

2921490002

3.2

2.98460

white solid

0.954g/cm3

141-142 °C

272.5ºC at 760mmHg

108.4ºC

soluble in water at 100mM

Store at RT

LD50 in rats (mg/kg): 81 i.v., 280 s.c. (Magyar)

D25 -10.8° (c = 6.48 in water)

141 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

MW: 187.28; monamine oxidase B inhibitor; oil; bp = 92-93 °C at 0.8 mm Hg /Selegiline/|Oil; bp = 103+110 °C at 5 mm Hg /Selegiline (+/-)form/

III

6.1(b)

3249

3

22-36

DA0292500

P234, P260, P261, P264, P270, P271, P273, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P314, P321, P330, P332+P313, P362, P390, P391, P404, P501

H290

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl selegiline hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Danger|H290 (20%): May be corrosive to metals [Warning Corrosive to Metals]|P234, P260, P261, P264, P270, P271, P273, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P314, P321, P330, P332+P313, P362, P390, P391, P404, and P501|Aggregated GHS information provided by 5 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Although some patients appear to be sensitive to the hypertensive effects of sympathomimetic agents during therapy with a nonselective MAO inhibitor, nonprescription (over-the-counter, OTC) or prescription cold or hay fever preparations that contain pressor agents (e.g., ephedrine, phenylpropanolamine) generally can be given to patients receiving selegiline hydrochloride dosages of 10 mg or less daily without undue risk of uncontrolled hypertension. However, hypertensive crisis was reported in at least one patient receiving the recommended 10 mg daily dosage of selegiline hydrochloride and a sympathomimetic agent (ephedrine).|In patients receiving levodopa, addition of selegiline hydrochloride may exacerbate levodopa-associated dyskinesias. This effect, which occurred in an average of 28% (range: 4-90%) of patients receiving the drug in clinical trials, usually occurs within 2 weeks after initiating selegiline therapy and generally is mitigated when the levodopa dosage is reduced ... . Bruxism, muscle twitching and myoclonic jerks have occurred in patients receiving levodopa and selegiline hydrochloride dosages exceeding 10 mg daily.|Asystole, diaphoresis, hypertension, syncope, changes in behavior and mental status, impaired consciousness, hyperpyrexia, seizures, muscular rigidly, and tremors have occurred with concurrent use of selegiline and tricyclic antidepressants. Concurrent use is not recommended; at least 14 days should elapse between discontinuation of selegiline and initiation of a tricyclic antidepressant. /Selegiline/|A reaction resembling the serotonin syndrome has been reported rarely following concurrent use of selegiline with selective serotonin re-uptake inhibitors (SSRIs). (The serotonin syndrome may occur as the result of combining a serotonergic agent with an MAO inhibitor. The syndrome may be manifest by mental status changes (confusion, hypomania), restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, tremor, diarrhea, incoordination, and/or fever. If recognized early, the syndrome usually resolves quickly upon withdrawal of the offending agents.) Concurrent use of selegiline with SSRIs is not recommended because of the potential for autonomic instability, muscular rigidity, severe agitation, or delirium. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of an SSRI. However, because of the long half-lives of fluoxetine and its active metabolite, at least 5 weeks (approximately 5 half-lives) should elapse between discontinuation of fluoxetine and initiation of therapy with an MAO inhibitor. ALso, based on the half-life of venlafaxine, at least 7 days should elapse between discontinuation of venlafaxine and initiation of therapy with an MAO inhibitor. /Selegiline/|For more Interactions (Complete) data for SELEGILINE HYDROCHLORIDE (9 total), please visit the HSDB record page.

LD50 Rat sc 280 mg/kg|LD50 Rat iv 81 mg/kg

Monamine oxidase B inhibitor|Selegiline is indicated for use with levodopa or levodopa and carbidopa combination in the treatment of idiopathic Parkinson's disease (paralysis agitans). /Included in US product labeling/ /Selegiline/|.... we report briefly on neurotoxicity associated with the immunodeficiency virus and discuss the effects of selegiline, a monoamine oxidase inhibitor which enhances dopamine availability in CNS on immunodeficiency virus-induced neurological disease. ... /MAO inhibitors may be potent mediators of the neuropathological deficits in immunodeficiency virus infection and factors which may accelerate the progression of the immunodeficiency virus --neurological disease./|EXPTL Therapy: ... Twenty patients with mild-moderate pathological cerebral involution of atrophic and/or vascular origin, were treated with Selegiline (L-deprenyl), a monoamino-oxidase B inhibitor (10 mg/day for six months). Compared with a control group, Selegiline treated patients showed a statistically significant improvement in cognitive and behaviour capacities. At the end of investigation, "Mini Mental State" showed an improvement of 26.5% in Selegiline group and of 3.7% in control group (P < 0.01). "Echelle Clinique d'Aptitudes Intellectuelles" showed an improvement of 29.4% and of 10.8% respectively (P < 0.01). Selegiline treatment has shortened significantly the reaction times and has improved mnesic capacities. No side effects were observed during the study. /Selegiline/|For more Therapeutic Uses (Complete) data for SELEGILINE HYDROCHLORIDE (10 total), please visit the HSDB record page.

Pregnancy risk category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./|Selegiline may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.|Therapeutic use may lead to increased tremor, bradykinesia, falling, dystonic symptoms, dyskinesias, hallucinations, confusion, sleep disturbance, headache, dry mouth, blurred vision, orthostatic hypotension, hypertension, poor appetite, urinary retention, and diaphoresis. Hypomanic behavior may be due to the l-amphetamine and l-amphetamine metabolites of selegiline.|In patients receiving levodopa, addition of selegiline hydrochloride may exacerbate levodopa-associated dyskinesias. This effect, which occurred in an average of 28% (range: 4-90%) of patients receiving the drug in clinical trials, usually occurs within 2 weeks after initiating selegiline therapy and generally is mitigated when the levodopa dosage is reduced ... . Involuntary movements, increased tremor, chorea, loss of balance, freezing, blepharospasm, increased bradykinesia, facial grimacing, speech problems, heavy leg, stiff neck, tardive dyskinesia, dystonic manifestations, festination, increased apraxia, and muscle cramping may occur in patients receiving selegiline. Bruxism, muscle twitching and myoclonic jerks have occurred in patients receiving levodopa and selegiline hydrochloride dosages exceeding 10 mg daily.|For more Drug Warnings (Complete) data for SELEGILINE HYDROCHLORIDE (12 total), please visit the HSDB record page.

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. (See all compounds classified as Antidepressive Agents.)|Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists. (See all compounds classified as Antiparkinson Agents.)|Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. (See all compounds classified as Neuroprotective Agents.)|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) (See all compounds classified as Monoamine Oxidase Inhibitors.)

Selegiline and its metabolites are widely distributed into body tissues and cross the blood-brain barrier. Following IV administration of radiolabeled selegiline hydrochloride in mice, the parent drug and/or metabolites are rapidly and widely distributed to brain, liver, kidney, lung, heart, and brown fat. Following IV administration of radiolabeled selegiline hydrochloride in healthy adults, the highest accumulation of radioactivity occurred in the thalamus, basal ganglia, mesencephalon, and cingulate gyrus. /Selegiline/|Selegiline is excreted principally in urine as conjugated and unconjugated metabolites. About 20-63% of an orally administered dose of selegiline is excreted in urine as l-methamphetamine, 9-26% as l-amphetamine, and 1% as l-demethylselegiline. ... About 15% of a dose is excreted in feces within 72 hours following administration of selegiline. /SRP: This would usually result in a false positive drug test for d-methamphetamine if no d/l-isomer characterization was performed on the specimen./ /Selegiline/|Rapidly absorbed from the gastrointestinal tract.|... The mean peak plasma concentration (Cmax) is approximately 2 ug/L and the time to reach the peak is under an hour. The absolute bioavailability of selegiline is approximately 10%. It has an apparent volume of distribution of 1854 L. The oral clearance of selegiline (59 L/min) is many fold higher than the liver blood flow (1.5 L/min), indicating that extrahepatic processes are involved in the elimination of selegiline. ... /Selegiline/|... Selegiline is readily absorbed from the gastrointestinal tract and rapidly enters the brain and spinal cord following oral administration. The drug binds to brain regions with a high MAO-B content, such as the thalamus, the striatum, the cortex, and the brainstem. ... /Selegiline/

Selegiline is excreted principally in urine as conjugated and unconjugated metabolites. About 20-63% of an orally administered dose of selegiline is excreted in urine as l-methamphetamine, 9-26% as l-amphetamine, and 1% as l-demethylselegiline. /Selegiline/|Rapidly and completely metabolized to N-desmethyldeprenyl, l-methamphetamine, and l-amphetamine.|Selegiline is extensively metabolized, presumably through cytochrome p450 mediated oxygenation, to form l-desmethylselegiline and l-methamphetamine, which is further metabolized to l-amphetamine. Selegiline also is metabolized in the lungs to l-desmethylselegiline and l-methamphetamine and in the kidneys to l-methamphetamine, but the degree of metabolism in these tissues is minimal compared with that in the liver. /Selegiline/|... The pharmacokinetics of selegiline are highly variable. Following an oral dose of selegiline 10 mg, it is rapidly absorbed and metabolized to desmethylselegiline, levoamphetamine and levomethamphetamine. /Selegiline/|For more Metabolism/Metabolites (Complete) data for SELEGILINE HYDROCHLORIDE (6 total), please visit the HSDB record page.

Elimination: Selegiline: 39 (range, 16 to 69) hours. /Selegiline/|The mean half-lives of the 3 active metabolites that were found in serum and urine following a single dose of selegiline are as follows: N-desmethyldeprenyl, 2 hours; l-amphetamine, 17.7 hours; l-methamphetamine, 20.5 hours. /Selegiline/

The action of selegiline is thought to be related to its irreversible inhibition of monoamine oxidase type B (MAO B), the major form of the enzyme in the human brain. MAO B, which is involved in the oxidative deamination of dopamine in the brain, is inhibited when selegiline binds covalently and stoichiometrically to the isoalloxazine flavin adenine dinucleotide (FAD) at its active center. Administration of 10 mg of selegiline a day produces almost complete inhibition of MAO B in the brain. Selegiline becomes a nonselective inhibitor of all monamine oxidase (MAO) at higher doses, possibly at 20 to 40 mg a day. At these doses, tyramine-mediated hypertensive reaction with MAO A blockade ("cheese reactions") may occur. /Selegiline/|Selegiline (or its metabolites) may also act through other mechanisms to increase dopaminergic activity, including interfering with dopamine reuptake at the synapse. /Selegiline/|The mechanism of action of selegiline is complex and cannot be explained solely by its MAO-B inhibitory action. Pretreatment with selegiline can protect neurons against a variety of 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-beta-acetoxyethyl-2-chloroethylamine (AF64A), and 5,6-dihydroxyserotonin, which damage dopaminergic, adrenergic, cholinergic, and sertoninergic neurons, respectively. Selegiline produces an amphetamine-like effect, enhances the release of dopamine, and blocks the reuptake of dopamine. It stimulates gene expression of L-aromatic amino acid decarboxylase, increases striatal phenylethylamine levels, and activates dopamine receptors. Selegiline reduces the production of oxidative radicals, up-regulates superoxide dismutase and catalase, and suppresses nonenzymatic and iron-catalyzed autooxidation of dopamine. Selegiline compensates for loss of target-derived trophic support, delays apoptosis in serum-deprived cells, and blocks apoptosis-related fall in the mitochondrial membrane potential. Most of the aforementioned properties occur independently of selegiline's efficacy to inhibit MAO-B. /Selegiline/|Selegiline is a selective inhibitor of monoamine oxidase-B (MAO-B) at a dose of 10 mg/day and is given to patients with Parkinson's disease as an adjunct to levodopa therapy. By inhibiting MAO-B, selegiline increases the dopamine levels in the substantia nigra. Selegiline also blocks dopamine re-uptake from the synaptic cleft, thus increasing the dopamine concentrations in the brain. ... /Selegiline/|For more Mechanism of Action (Complete) data for SELEGILINE HYDROCHLORIDE (6 total), please visit the HSDB record page.

Patients who have ingested an overdose of selegiline should be immediately admitted to a hospital, where blood pressure, body temperature, and fluid and electrolyte balance may be closely monitored. Instillation of a charcoal slurry under airway protection may be useful in early poisoning. Signs and symptoms of central nervous system stimulation, including seizures, should be treated with intravenous diazepam. Phenothiazine derivatives and central nervous system stimulants should be avoided. Hypotension and vascular collapse should be treated with intravenous fluids and, if necessary, a pressor agent. Adrenergic agents may induce a markedly increased pressor response. Respiration should be supported by airway management, use of supplemental oxygen, and mechanical ventilatory assistance as required. It is unlikely that extracorporeal methods to enhance elimination (hemodialysis, hemoperfusion) will be effective (high protein binding, extensive volume of distribution). Treatment is largely symptomatic and supportive. There is no antidote. /Selegiline/|Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/|Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat hypertension, hypotension, coma, seizures, and hyperthermia if they occur. Continuously monitor temperature, other vital signs, and ECG for a minimum of 6 hours in asymptomatic patient, and admit all symptomatic patients for continuous monitoring for 24 hours. Since the hypertension is catecholamine-mediated, alpha-adrenergic blockers (e.g., phentolamine) or combined alpha- and beta-adrenergic blockers (e.g., labetalol) are particularly useful. /MAO Inhibitors/|For more Antidote and Emergency Treatment (Complete) data for SELEGILINE HYDROCHLORIDE (6 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ Signs and symptoms of overdose may include drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonus, seizures and coma, rapid and irregular pulse, hypertension, hypotension and vascular collapse, precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cold, clammy skin.|/SIGNS AND SYMPTOMS/ Overdoses are likely to cause significant inhibition of both MAO-A and MAO-B. Signs and symptoms of overdose may resemble those observed with nonselective MAOIs, for example tranylcypromine (Parnate), isocarboxazid (Marplan), and phenelzine (Nardil). Death has been reported following overdose.|/SIGNS AND SYMPTOMS/ At least one interaction of meperidine with selegiline has been reported; concurrent use of meperidine with nonselective monoamine oxidase inhibitors (MAOIs) may produce immediate excitation, sweating, rigidity, and severe hypertension; in some patients, hypotension, severe respiratory depression, coma, convulsions, hyperpyrexia, vascular collapse, and death may occur; avoidance of meperidine use within 2 to 3 weeks following MAO inhibition is recommended; other opioid analgesics such as morphine are not likely to cause such severe reactions and may be used cautiously in reduced dosage in patients receiving MAOIs; however, it is recommended that a small test dose (one quarter of the usual dose) or several small incremental test doses over a period of several hours should first be administered to permit observation of any adverse effects; caution is also recommended in the use of alfentanil, fentanyl, or sufentanil as an adjunct to anesthesia if the patient has received an MAOI within 14 days; because the risk of a significant interaction has been questioned, the use of a small test dose is advised to detect any possible interaction. /Selegiline/|/SIGNS AND SYMPTOMS/ Asystole, diaphoresis, hypertension, syncope, changes in behavior and mental status, impaired consciousness, hyperpyrexia, seizures, muscular rigidly, and tremors have occurred with concurrent use of selegiline and tricyclic antidepressants. Concurrent use is not recommended; at least 14 days should elapse between discontinuation of selegiline and initiation of a tricyclic antidepressant. /Selegiline/|/CASE REPORTS/ We report here the case of a patient with fluoxetine and selegiline induced serotonin syndrome, which presented as encephalopathy, generalized myoclonas, fever, stiffness and sweating, complicated with acute renal failure, rhabdomyolysis and disseminated intravascular coagulation findings. The patient died 6 days after admission. /Selegiline/

Deprenalin

Selegiline hydrochloride: Oral: Capsules, 5 mg, Eldepryl (Somerset); Tablets, 5 mg, Atapryl (Athena Neurosciences), Carbex (Endo), Selpak (Modulus).|/Trade Names:/ Anipryl; Antiparkin; Atapryl; Amindan; Carbex; Deprenyl; Eldeprine; Eldepryl; Jumex; Movergan; Plurimen; Selepark; Seletop; Zelapar.

Analyte: selegiline hydrochloride; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: selegiline hydrochloride; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|Analyte: selegiline hydrochloride; matrix: chemical identification; procedure: retention time of liquid chromatogram with comparison to standards|Analyte: selegiline hydrochloride; matrix: chemical identification; procedure: visual reaction (white, curdy precipitate) with silver nitrate (Chloride test)|For more Analytic Laboratory Methods (Complete) data for SELEGILINE HYDROCHLORIDE (7 total), please visit the HSDB record page.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients