아만타딘

Pharmaceuticals

Pharmaceuticals -> Listed in ZINC15

log Kow = 2.44

2.3

2.54

Stable, white or nearly white crystalline powder. Crystals from abs ethanol+ anhydr ether. Decomp at 360 °C. Practically insol in ether; sol in water (at least 1:20). /Hydrochloride/

Sparingly sol in water

8.46e-02 g/L

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antiparkinson Agents; Antiviral Agents; Dopamine Agents

FDA approved drugs -> Active ingredient

Pharmaceuticals

180-192

160-190 °C (closed tube); Also reported as 180-192 °C

180 °C

10.58

10.68

ODORLESS; BITTER TASTE; DOES NOT MELT UP TO 300 °C, BUT SUBLIMES SLOWLY; PKA: 10.36 AT 30 °C; PH (1 IN 5 SOLN) BETWEEN 3.0 & 5.5. WHITE OR NEARLY WHITE CRYSTALLINE POWDER; 1 G IN 2.5 ML WATER, 5.1 ML ALCOHOL, 18 ML CHLOROFORM, 70 ML POLYETHYLENE GLYCOL 400 /AMANTADINE HYDROCHLORDIE/

Danger

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P351+P338, P305+P354+P338, P316, P317, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P363, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 156 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Tricyclo[3.3.1.13,7]decan-1-amine

REACH registered substance: Amantadine (EC: 212-201-2)

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

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

There is no specific antidote for an overdose of Amantadine. However, slowly administered intravenous physostigmine in 1 and 2 mg doses in an adult2 at 1- to 2-hour intervals and 0.5 mg doses in a child3 at 5- to 10-minute intervals up to a maximum of 2 mg/hour have been reported to be effective in the control of central nervous system toxicity caused by amantadine hydrochloride. For acute overdosing, general supportive measures should be employed along with immediate gastric lavage or induction of emesis. Fluids should be forced, and if necessary, given intravenously. The pH of the urine has been reported to influence the excretion rate of Amantadine. (L1744)

The anti-influenza A activities of amantadine and ribavirin were investigated seperately and in combination. In ferret tracheal ciliated epithelium, the combination of drugs synergistically delayed the virus-induced cytopathic effect.

Concurrent use /of alcohol/ with amantadine is not recommended since this may increase the potential for CNS effects such as dizziness, lightheadedness, orthostatic hypotension, or confusion.

Concurrent use /of anticholinergics, or other medications with anticholinergic activity; tricyclic antidepressants; other antidyskinetics; antihistamines; or phenothiazines/ with amantadine may potentiate the anticholinergic-like side effects, especially those of confusion, hallucinations, and nightmares; dosage adjustments of these medications or of amantadine may be necessary; also, patients should be advised to report occurrences of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy.

Concurrent use /of opioid- and anticholinergic-containing antidiarrheals/ with amantadine may potentiate the anticholinergic-like side effects; although significant interaction is unlikely with usual doses of opioid- and anticholinergic-containing antidiarrheals, significant interaction may occur if these medications are abused.

For more Interactions (Complete) data for AMANTADINE (10 total), please visit the HSDB record page.

Acute overdosage of amantadine has resulted in cardiac dysfunction (e.g., arrhythmia, tachycardia, hypertension); pulmonary edema and respiratory distress (including adult respiratory distress syndrome); renal dysfunction (e.g., increased BUN, decreased creatinine clearance, renal insufficiency); or CNS toxicity (e.g., insomnia, anxiety, psychotic reactions, lethargy, somnolence, coma). Hyperthermia also has occurred with amantadine overdosage. In addition, seizures may be exacerbated in patients with a history of a seizure disorder (A620).

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

N04BB01

N - Nervous system

QN - Nervous system

Amantadine is an antiviral drug which also acts as an antiparkinson agent, for which it is usually combined with L-DOPA when L-DOPA responses decline (probably due to tolerance). It is a derivate of adamantane, like a similar drug rimantadine. The mechanism of action of amantadine in the treatment of Parkinson's disease and drug-induced extrapyramidal reactions is not known. It has been shown to cause an increase in dopamine release in the animal brain, and does not possess anticholinergic activity.

The mechanism of its antiparkinsonic effect is not fully understood, but it appears to be releasing dopamine from the nerve endings of the brain cells, together with stimulation of norepinephrine response. It also has NMDA receptor antagonistic effects. The antiviral mechanism seems to be unrelated. The drug interferes with a viral protein, M2 (an ion channel), which is needed for the viral particle to become "uncoated" once it is taken inside the cell by endocytosis.

Amantadine, like rimantadine, inhibits viral replication by interfering with the influenza A virus M2 protein, an integral membrane protein. The M2 protein of influenza A functions as a ion channel and is important in at least 2 aspects of virus replication, disassembly of the infecting virus particle and regulation of the ionic environment of the transport pathway. By interfering with the ion channel function of the M2 protein, amantadine inhibits 2 stages in the replicative cycle of influenza A. Early in the virus replicative cycle, amantadine inhibits uncoating of the virus particle, presumably by inhibiting the acid-mediated dissociation of the virion nucleic acid and proteins, which prevents nuclear transport of viral genome material. Amantadine also prevents viral maturation in some strains of influenza A (e.g., H7 strains) by promoting pH-induced conformational changes in influenza A hemagglutinin during its intracellular transport late in the replicative cycle. Adsorption of the virus to and penetration into cells do not appear to be affected by amantadine. In addition, amantadine does not interfere with the synthesis of viral components (e.g., RNA-directed RNA polymerase activity).

The mechanism of action of amantadine in the treatment of Parkinson's disease and drug-induced extrapyramidal reactions is not known. Data from earlier animal studies suggest that symmetrel may have direct and indirect effects on dopamine neurons. More recent studies have demonstrated that amantadine is a weak, non-competitive NMDA receptor antagonist (Ki = 10 uM). Although amantadine has not been shown to possess direct anticholinergic activity in animal studies, clinically, it exhibits anticholinergic-like side effects such as dry mouth, urinary retention, and constipation.

The mechanism by which amantadine exerts its antiviral activity is not clearly understood. It appears to mainly prevent the release of infectious viral nucleic acid into the host cell by interfering with the function of the transmembrane domain of the viral M2 protein. In certain cases, amantadine is also known to prevent virus assembly during virus replication. It does not appear to interfere with the immunogenicity of inactivated influenza A virus vaccine.

In isolated ventricular muscle preparations (frog, rabbit, cat, dog, and calf) amantadine increased the action potential duration, decreased the amplitude and max diastolic potential, and induced phase 4 depolarization. These changes may be due to the effect of amantadine on potassium ion conductance.

Mean half-lives ranged from 10 to 14 hours, however renal function impairment causes a severe increase in half life to 7 to 10 days.

Amantadine pharmacokinetics were determined in 24 normal adult male volunteers after the oral administration of a single amantadine hydrochloride 100 mg soft gel capsule. ... The half-life was 17 + or - 4 hours (range: 10 to 25 hours). Across other studies, amantadine plasma half-life has averaged 16 + or - 6 hours (range: 9 to 31 hours) in 19 healthy volunteers.

Normal renal function: 11 to 15 hours. Elderly patients: 24 to 29 hours. Renal function impairment, severe: 7 to 10 days. Hemodialysis: 24 hours.

The elimination half-life increases two to three fold or greater when creatinine clearance is less than 40 mL/min/1.73 sqm and averages eight days in patients on chronic maintenance hemodialysis.

No appreciable metabolism, although negligible amounts of an acetyl metabolite have been identified.

Eight metabolites of amantadine have been identified in human urine. One metabolite, an N-acetylated compound, was quantified in human urine and accounted for 5-15% of the administered dose. Plasma acetylamantadine accounted for up to 80% of the concurrent amantadine plasma concentration in 5 of 12 healthy volunteers following the ingestion of a 200 mg dose of amantadine. Acetylamantadine was not detected in the plasma of the remaining seven volunteers..

No appreciable metabolism, although negligible amounts of an acetyl metabolite have been identified. Amantadine is well absorbed orally from the gastrointestinal tract. The mechanism of its antiparkinsonic effect is not fully understood, but it appears to be releasing dopamine from the nerve endings of the brain cells, together with stimulation of norepinephrine response. The antiviral mechanism seems to be unrelated. The drug interferes with a viral protein, M2 (an ion channel), which is needed for the viral particle to become "uncoated" once it is taken inside the cell by endocytosis. Metabolites are excreted in the urine (A308). Route of Elimination: It is primarily excreted unchanged in the urine by glomerular filtration and tubular secretion. Half Life: Mean half-lives ranged from 10 to 14 hours, however renal function impairment causes a severe increase in half life to 7 to 10 days.

BF4C9Z1J53

AMANTADINE

Established Pharmacologic Class [EPC] - Influenza A M2 Protein Inhibitor

Mechanisms of Action [MoA] - M2 Protein Inhibitors

Amantadine is an Influenza A M2 Protein Inhibitor. The mechanism of action of amantadine is as a M2 Protein Inhibitor.

AMANTADINE

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.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.

Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.

A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.

Amantadine is well absorbed orally from the gastrointestinal tract.

It is primarily excreted unchanged in the urine by glomerular filtration and tubular secretion.

3 to 8 L/kg [healthy subjects]

0.2 - 0.3 L/hr/kg

Rapidly and almost completely absorbed from gastrointestinal tract.

Amantadine is distributed into breast milk.

MEDICATION (VET)

Used as a chemical intermediate for the synthesis of tromantadine.

Antiviral and treatment for Parkinson's disease

Analgesics, Non-Narcotic; Antiparkinson Agents; Antiviral Agents; Dopamine Agents

Prevent infection with various strains of influenza A virus.

Use (kg; approx.) in Germany (2009): >2500

Amantadine is brominated to 1-bromo compound, which is then reacted with acetonitrile in presence of sulfuric acid to produce n-(1-adamantanyl)acetamide. Alkaline hydrolysis liberates amantadine, which is reacted with hydrogen chloride in suitable solvent to yield official salt. /amantadine hydrochloride/

1-Bromoadamantane + acetonitrile (Ritter reaction)

Oral: Capsules, liquid-filled Tablets: 100 mg (available by nonpropriety name), 100 mg, Symmetrel, (Endo); Solution: 50 mg/5 mL, Symmetrel Syrup ( with parabens), (Endo).

Trade Names.Hydrochloride: Amazolon (Sawai), Mantadine (Du Pont), Mantadix (Du Pont, Rhône-Poulenc), Symmetrel (Ciba-Geigy), Virofral (Ferrosan). Sulfate: Contenton (SKD), PK-Merz (Merz).

administered PO, intranasal, SC, IP, or aerosol routes.

Tricyclo[3.3.1.13,7]decan-1-amine: ACTIVE

Available commercially as the free base or the hydrochloride, sulfate, or fumarate salts.