Amantadine

Structural formula
General
Non-proprietary name	Amantadine
other names	1-Tricyclo [3.3.1.1 3.7 ] decylamine ( IUPAC ) 1-adamantanamine Adamantan-1-ylamine 1-adamantylazane Tricyclo [3.3.1.1 3.7 ] decan-1-ylazane
Molecular formula	C 10 H 17 N
External identifiers / databases
CAS number 768-94-5 (amantadine) 665-66-7 (amantadine hydrochloride ) PubChem 2130 DrugBank DB00915 Wikidata Q409761
Drug information
ATC code	N04 BB01
Drug class	Antiviral NMDA antagonist
properties
Molar mass	151.25 g · mol -1
Physical state	firmly
Melting point	180 ° C
solubility	slightly soluble in water (6.29 g l −1 at 25 ° C)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Caution H and P phrases H: 302 P: no P-phrases
Toxicological data	900 mg kg −1 ( LD 50 ,  rat ,  oral , amantadine)
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Amantadine is a derivative of adamantane . It is used as a medicine to treat the flu caused by influenza A viruses and to treat Parkinson's syndrome .

Clinical information

Amantadine is a drug that for the treatment of the influenza A virus induced influenza is suitable. In therapeutic doses, amantadine can shorten the duration of fever of type A influenza by about one day. Due to common side effects such as B. diarrhea , depression , epileptic fits, tachycardia and peripheral edema , this drug is rarely used.

Amantadine is also used in Parkinson 's therapy. It weakens the overactivity of acetylcholinergic striatal interneurons that occurs in Parkinson's disease and, as a weak NMDA receptor antagonist, slows down the influence of glutamatergic projections from the cortex. In addition, amantadine has an indirect agonistic effect on dopamine receptors in the brain (in the striatum ) by increasing dopamine release and by inhibiting dopamine reuptake in the presynaptic nerve cells . According to proponents of the product, it is beneficial to exercise and drive and, in their opinion, is a good addition to other drugs (especially L-Dopa ) in treatment. It is the drug of choice in the so-called akinetic crisis, a life-threatening condition with movement blocks lasting hours or days, a high fever and profuse sweating. Advocates of evidence-based medicine consider a positive effect beyond placebo in Parkinson's disease to be insufficiently proven. Amantadine is mostly used in the advanced stages of Parkinson's disease. There are now numerous generic preparations on the market.

A possible positive effect in the treatment of withdrawal symptoms of cocaine addicts is also under discussion. However, clear - scientifically sound - evidence for this thesis cannot be granted to date.

Amantadine was also used to treat fatigue in multiple sclerosis , but in May 2011 the G-BA declared it ineffective for fatigue.

Furthermore, outside of the approval, amantadine is used for impaired consciousness after brain injury, with the idea of increasing the arousal through the dopaminergic effects . Smaller studies sometimes showed positive effects, with the onset, duration and disease present differing greatly in the studies.

The drug is subject to medical prescription in Germany and Austria .

Pharmacological properties

Mechanism of action

Amantadine has an inhibiting effect on the uncoating , i.e. H. on the release of the viral genetic information into the cytoplasm of the host cell. Amantadine blocks the M2 ion channel protein contained in the shell . However, this effect is only achieved in the case of influenza A viruses with therapeutic doses of the active ingredient. Influenza virus type B and other enveloped virus forms are only inhibited at concentrations beyond the therapeutic range . With some RNA viruses, amantadine hydrochloride prevents penetration and 'uncoating', i. H. the release of the viral nucleic acid.

Amantadine is a weak antagonist of the NMDA receptor (glutamate receptor subtype), increases the release of dopamine and blocks dopamine reuptake. This allows a weak effectiveness in the context of Parkinson's therapy. It is also used in drug-induced parkinsonism or in combination with L-DOPA to treat L-DOPA-related dyskinesias.

Side effects

• Impairments of perception and mood, e.g. B. Depression , euphoria, confusion, hallucinations, and nightmares (uncommon)
• Urination disorders (micturition disorders) (uncommon)
• Difficulty sleeping (uncommon)
• Blood pressure disorder (uncommon)
• Nausea, vomiting, diarrhea (uncommon)
• Rhabdomyolysis (uncommon)
• Livedo reticularis , sometimes associated with edema in the lower leg and ankle area (common)

Other Information

In 2005, the active ingredient was administered to poultry in large quantities (approx. 2.6 million doses) in Southeast Asia , in the belief that it could protect against the influenza A virus H5N1 . The virus strains there are, however, resistant to amantadine . In western countries, the use of amantadine in veterinary medicine is prohibited.

Trade names

Monopreparations

Amant (A), Amixx (D), Hofcomant (A), PK-Merz (D, A, CH), Symmetrel (CH), tregor (D), numerous generics (D, A)

Individual evidence

1. ↑ ^{a b} J. Kornhuber, J. Bormann, M. Hübers, K. Rusche, P. Riederer: Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study. In: Eur.J.Pharmacol.Mol.Pharmacol.Sect. 206, 1991, pp. 297-300. PMID 1717296
2. ↑ ^{a b c} Entry on amantadine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
3. ↑ ^{a b} Amantadine hydrochloride data sheet from Sigma-Aldrich , accessed on March 20, 2011 ( PDF ).
4. ^ Guidelines of the German Society for Neurology. Extrapyramidal motor disorders. Parkinson's Syndromes. In: Guidelines for Diagnostics and Therapy in Neurology. 3rd, revised edition. Georg Thieme Verlag, Stuttgart 2005, ISBN 3-13-132413-9 , AWMF online - S2 guideline neurology: Parkinson's syndrome .
5. ↑ NJ Crosby et al: Amantadine in Parkinson's disease. In: Cochrane Database Syst Rev. (1), 2003, Art. No. CD003468. PMID 12535476 .
6. ^ NJ Crosby et al.: Amantadine for dyskinesia in Parkinson's disease. In: Cochrane Database Syst Rev. (2), 2003, Art. No. CD003467. PMID 12804468 .
7. ↑ KM Kampman et al .: Amantadine in the treatment of cocaine-dependent patients with severe withdrawal symptoms. In: Am J Psychiatry. 157 (12), 2000, pp. 2052-2054. PMID 11097979 ; PDF (free full text, English).
8. ↑ FH Gawin et al .: Double-blind evaluation of the effect of acute amantadine on cocaine craving. In: Psychopharmacology (Berl). 97 (3), 1989, pp. 402-403. PMID 2497490 .
9. ↑ Giulia Cossu: Therapeutic options to enhance coma arousal after traumatic brain injury: State of the art of current treatments to improve coma recovery. In: British Journal of Neurosurgery. 28, 2014, p. 187, doi: 10.3109 / 02688697.2013.841845 .
10. ↑ Ordinance of the Federal Minister for Health and Environmental Protection of August 30, 1973 on prescription drugs (Prescription Ordinance) , version of October 27, 2014.
11. ↑ K. Aktories and others: Pharmacology and Toxicology. 9th edition. Urban & Fischer at Elsevier, 2006, ISBN 3-437-44490-5 .
12. ^ Viruses and General Virology. In: olivernolte.de. Retrieved July 28, 2016 . 
13. ^ Douglas C. Blood, Virginia P. Studdert, Clive C. Gay: Saunders Comprehensive Veterinary Dictionary . 3. Edition. Saunders, 2006, ISBN 978-0-7020-3238-7 .
14. ↑ Summary of investigation results - Amantadine hydrochloride. (PDF; 22 kB) Pharmaceuticals and Medical Devices Agency , September 15, 2015, accessed on July 28, 2016 (English). 
15. ↑ Alan Sipress: Bird Flu Drug Rendered Useless. In: Washington Post online. 18th of June. 2005, p. A01.

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