Memantine indications

The ChE inhibitors all have the indication for the treatment of mild to moderate dementia of the Alzheimer s type. Guidelines for the treatment of AD were written before the approval of memantine and recommend the use of ChE inhibitors as a valuable treatment for AD.27-29 None of the ChE inhibitors have been compared in head-to-head studies, so the decision to use one over another is based on differences in mechanisms of action, adverse reactions, and titration schedules. 

In vitro studies have shown that memantine produces minimal inhibition of CYP450 enzymes CYP1A2, 2A6, 2C9,2D6, 2E1, and 3A4. These data indicate that no pharmacokinetic interactions with drugs metabolized by these enzymes should be expected.38... 

The side effects of memantine are generally mild and include headache, dizziness, and constipation. Memantine is started at an initial dose of 5 mg each morning and is increased to 5 mg twice daily after 1 week. The maximum dose of memantine is 10 mg taken twice daily. A recent study indicates that memantine works syner-gistically with cholinesterase inhibitors (see Section 10.5.5), and it has quickly become routine clinical practice to coadminister memantine with one of these agents. 

Amantadine has a long history in the symptomatic treatment of Parkinson s disease. Several recent double-blind, placebo-controlled studies have confirmed the impressive acute antidyskinetic effects of amantadine (Rajput et al. 1998 Verhagen Metman et al. 1998 Luginger et al. 2000 Del Dotto et al. 2001 Shoghi-Jadid et al. 2002). One study also indicates that amantadine s antidyskinetic benefit is maintained for at least 1 year (Metman et al. 1999). The related compound memantine was found, as in the MPTP monkey, to have no effect on dyskinesia in a double-blind study but it did improve parkinsonian symptoms (Merello et al. 1999). This indicates that the antidyskinetic effects of amantadine may be unrelated to NMDA receptor antagonism (Danysz et al. 1997). 

It is beheved that phenomena such as sensitization, tolerance and drug-dependence might also involve synaptic plasticity. In fact, numerous studies indicate that NMDA receptor antagonists block sensitization to amphetamine and cocaine as well as tolerance and dependence to ethanol and opioids in animal models (Trujillo and Akil 1991 Pasternak and Inturrisi 1995 Trujillo and Akil 1995 Mao 1999). Recent studies indicate that the uncompetitive NMDA receptor antagonists dextromethorphan, memantine and neramexane not only prevent the development of morphine tolerance, but also reverse estabhshed tolerance in the continuing presence of this opioid, prevent the expression of withdrawal symptoms in rats (Popik and Skolnick 1996 Popik and Danysz 1997 Popik and Kozela 1999 Houghton et al. 2001) and attenuate the expres-... 

In contrast to cholinesterase inhibitors, which are indicated tor mild to moderate Alzheimer disease, memantine is indicated tor moderate to severe Alzheimer disease Recently approved in the U.S. but available for many years in other countries (e.g., Germany)... 

A study conducted in Germany indicates that kava may have neuroprotective properties, primarily owing to its constituent methysticum and dihydromethysticum (18). The investigators studied the effects of kava extract WS 1490 and the individual pyrones kavain, dihydrokavain, methysticin, dihydromethysticin, and yangonin on the size of infarction in mouse brains. The extract as well as the individual pyrones methysticin and dihydromethysticin showed significant reductions in infarct area similar to those produced by memantine, an anticonvulsive agent known to have neuroprotective qualities (18). 

I Memantine. Memantine, an NMDA-antagonist, is a novel agent for treating AD. By blocking NMDA receptors, excitotoxic reactions, which ultimately lead to cell death, may be prevented. Memantine has been studied in patients with vascular dementia, and in patients with moderate and severe AD as monotherapy and in combination with donepezil with favorable results. It is currently indicated for use in AD patients with moderate to severe illness. 

Memantine, a NMDA receptor blocker that neutralizes the effect of glutamate at striatal and subthalamic levels, has shown beneficial effects in the treatment of some parkinsonian patients chronically treated with levodopa, who demonstrated increased motor deterioration. In addition, it is indicated for treatment of moderate to severe dementia of Alzheimer s disease (AD). 

The previously mentioned clinical studies indicate that memantine and donepezil can be safely coadministered, with no significant effects on the pharmacokinetic profile... 

The results of in vitro studies indicate that memantine is not likely to cause interactions via induction or inhibition of the major cytochrome P450 isoenzymes involved in drug metabolism (CYP1A2, CYP2C9, CYP3A4). In addition, memantine is not metabolised by this enzyme system, and is therefore not expected to undergo interactions via this mechanism. ... 

In pharmacology, two adamantane derivatives. Amantadine (1-adaman-taneamine hydrochloride) and Rimantadine (a-methyl-1-adamantane methy-lamine hydrochloride) have been well known because of their antiviral activity (Figure 3.5). The main indication of these drugs is prophylaxis and treatment of influenza A viral infections. They are also used in the treatment of Parkinsonism and inhibition of hepatitis C virus (HCV) [27]. Memantine (l-amino-3,5-dimethyladamantane) has been reported effective in slowing the progression of Alzheimer s disease [27]. 

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