Amantadine and Rimantadine
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
The most commonly encountered side effects of amantadine are CNS symptoms such as nervousness, difficulty in concentration, confusion, insomnia, light-headedness, dizziness, tremor, slurred speech, ataxia, drowsiness, depression, hallucinations, and headache; these symptoms are reported by up to 11–33% of young adults who take amantadine at a dose of 100 mg twice daily (Bryson et al., 1980; Hayden et al., 1981; Snoey and Bessen, 1990). In contrast, in some clinical trials using amantadine for prophylaxis or in volunteer studies, at a dose of 200 mg daily, the frequency of side effects has been in the order of 7–10% (Couch and Jackson, 1976; Delker et al., 1980). Psychiatric syndromes rarely associated with amantadine include frank psychosis (Smith, 2008), mania (Rego and Giller, 1989), and a single case of pathologic jealousy (Othello syndrome) in a patient receiving amantadine that was ascribed to the drug (McNamara and Durso, 1991). In addition, two cases of peripheral neuropathy attributed to amantadine have been reported (Shulman et al., 1999; Swerdloff and Tarras, 2000).
Drug therapy
Jeremy Playfer, John Hindle, Andrew Lees in Parkinson's Disease in the Older Patient, 2018
Amantadine is an unusual drug. Its anti-parkinsonian effect was discovered by chance when it was being used as an anti-viral agent.46 Pharmacologically amantadine resembles anticholinergic drugs. It also appears to have effects modulating dopamine re-uptake and the releasing of dopamine stores. More recently amantadine has been shown to have anti-NMDA receptor activity, blocking the action of glutamate within the basal ganglia circuitry.47 There are reports that it may be beneficial in reducing levodopa-induced dyskinesias.48 The recommended dose for amantadine is 100 mg daily, increased after one week to 100 mg twice daily to a maximum of 400 mg. The drug must be used in caution with the elderly and a daily dose over 200 mg has a significant risk of psychiatric side effects. Amantadine is best used as adjunct therapy. It can give a short-term boost to anti-Parkinson treatments on special occasions for the patient. There are many cautions and potential interactions with this drug. In particular, it should be avoided in patients with hepatic or renal impairment. It may cause significant fluid retention. Gastro-intestinal disturbances, insomnia and anxiety, vasculitis (livedo reticularis) and visual disturbance are side effects which frequently curtail the use of amantadine. In longer-term use it is difficult to withdraw and side effects such as weight loss, cognitive impairment and hallucinations become more evident.
Pathophysiology
Ibrahim Natalwala, Ammar Natalwala, E Glucksman in MCQs in Neurology and Neurosurgery for Medical Students, 2022
The history and findings are typical of Parkinson’s disease.9 Amantadine is a drug that can be used in the treatment of both Parkinson’s and influenza A. It blocks viral penetration as well as uncoating of the influenza virus and releases dopamine from intact nerve terminals. Since Parkinson’s disease is highly associated with decreased dopamine levels, amantadine is useful in these patients. Side effects of amantadine include ataxia, dizziness and slurred speech.10 It should be remembered that amantadine is not a first-line drug in the treatment of Parkinson’s disease.
Amantadine for the treatment of childhood and adolescent psychiatric symptoms
Published in Baylor University Medical Center Proceedings, 2021
Kyle Morrow, Sun Choi, Keith Young, Makram Haidar, Cassandra Boduch, James A. Bourgeois
Amantadine hydrochloride, an indirect dopamine agonist and N-methyl-D-aspartate receptor antagonist, can modulate symptoms of childhood psychiatric disorders.1–4 Multiple studies have reported effective off-label use of amantadine in attention deficit/hyperactivity disorder (ADHD) and as an augmenting agent in treatment-resistant unipolar depression, autism spectrum disorder, and obsessive-compulsive disorder.5–13 Common side effects of amantadine include nausea, dizziness, and insomnia.14 Rare side effects include psychosis, hypertension, livedo reticularis, and rash.15 Stimulants and nonstimulants used to treat ADHD are associated with more severe side effects, while antipsychotics have been associated with weight gain, extrapyramidal symptoms, QTc prolongation, and sedation.16,17 Some studies report that amantadine can reverse weight gain induced by antipsychotics.18–23 This study was a retrospective chart review of children and adolescents prescribed amantadine to assess its tolerability and treatment outcomes for psychiatric symptoms.
Amantadine reduces persistent fatigue during post-acute withdrawal phase in methamphetamine abstained individuals: A randomized placebo-controlled trial
Published in Journal of Substance Use, 2018
Atieh Modarresi, Kaveh Eslami, Leila Kouti, Reza Hassanvand, Mohammadreza Javadi, Mehdi Sayyah
The majority of research conducted to date on the efficacy of amantadine in stimulant withdrawal has been related to cocaine, however with no consistent findings (Alterman et al., 1992; Kampman, Volpicelli, Alterman, Cornish, & O’Brien, 2000). Amantadine enhances dopamine and norepinephrine release from neuronal storage sites that are depleted by chronic stimulant use (Alterman et al., 1992; Tennant & Sagherian, 1987). It also possesses NMDA antagonistic properties which are associated with neuroprotection and reducing the risk of relapse (Alterman et al., 1992; Ciccarone, 2011; Hubsher, Haider, & Okun, 2012; Romach et al., 2004; Tennant & Sagherian, 1987). Given the favorable mechanisms of amantadine for the treatment of stimulant withdrawal symptoms and its promises for the treatment of fatigue, this randomized controlled trial aimed to assess the efficacy of amantadine in fatigue treatment in methamphetamine-abstained individuals.
The use of amantadine in patients with unresponsive wakefulness syndrome after severe cerebral hemorrhage
Published in Brain Injury, 2020
Yu Gao, Linlin Ma, Fang Liang, Yi Zhang, Lin Yang, Xuehua Liu, Jing Yang
Amantadine was first used in the treatment of influenza A virus in 1960. Currently, it is less commonly used for influenza treatment and widely used for the treatment of Parkinson’s disease (13). The mechanism of action of amantadine is not fully understood. Pharmacologically, it is an N-methyl-D-aspartic acid antagonist that acts on presynaptic receptors to increase dopamine release and block dopamine reabsorption (14). Adequate levels of synaptic dopamine release ensure the normal performance of a variety of physiological functions, including motor control, emotional and cognitive processes (15). In acute phases of traumatic brain injury, transient neuronal excitation is followed by a long-term state of lowered excitability, which involves the depletion of multiple neurotransmitters, including dopamine. Amantadine enhances dopamine-dependent nigrostriatal, midbrain and frontal striatum signaling, processes associated with consciousness, motivation and attention (6). It has been hypothesized that patients with cerebral hemorrhage may also have pathological processes similar to those seen in traumatic brain injury. The observed therapeutic effects of amantadine indicate that there is insufficient dopamine neurotransmitter present after cerebral hemorrhage.
Related Knowledge Centers
- Dopamine Agonist
- Drug Resistance
- Dyskinesia
- Influenza A Virus
- Nicotinic Antagonist
- Nmda Receptor Antagonist
- Parkinsonism
- Medication
- Mechanism of Action
- M2 Proton Channel