Memantine

Low affinity use-dependent NMDA recqrtor antagonists meet the criteria for safe administration into patients. Drugs like amantadine and memantine have modest effects on Parkinson s disease and are used as initial therapy or as adjunct to l-DOPA. Their adverse effects include dizziness, lethargy and sleep disturbance. 

Lipton SA (2006) Paradigm shift in neuroprotection by NMDA receptor blockade memantine and beyond. Nat Rev Drug Discov 5 160-170... 

In pharmacology, two adamantane derivatives. Amantadine (1-adamanta-neamine hydrochloride) and Rimantadine (a-methyl-1-adamantane methyla-mine hydrochloride) (see Fig. 24), have been well known because of their antiviral activity [129]. The main application of these drugs is prophylaxis (treatment to prevent the onset of a particular disease) and treatment of influenza-A viral infections. They are also used in the treatment of parkinsonism and inhibition of hepatitis-C virus. Memantine (1-amino-3,5-dimethyladaman-tane) (see Fig. 24) has been reported effective in slowing the progression of Alzheimer s disease [130]. 

The site of action for Memantine is the central nervous system (CNS) and it has CNS affinity. Amantadine and Rimantadine can penetrate to the CNS and cause some adverse effects. 

Figure 24. Chemical structures of (a) Amantadine, (b) Rimantadine, and (c) Memantine.

Nath A, Haughey NJ, Jones M, Anderson C, Bell JE, Geiger JD (2000) Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gpl20 protection by memantine. Ann Neurol 47(2) 186-194... 

Toggas SM, Masliah E, Mucke L (1996) Prevention of HIV-1 gpl20-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine. Brain Res 706 303-307... 

Antagonists L-AP3 MK-801 Memantine Ketamine Dextrophan CPP 7-CK (glycine site) CNQX NBQX LY382884... 

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. 

Data from product Information for tacrine, donepezil, rivastigmine, galantamine, and memantine.34-38... 

Memantine is a non-competitive antagonist oftheN-methyl-D-aspartate (NMDA) type of glutamate receptors, which are located ubiquitously throughout the brain. It regulates activity... 

Data from Product Information tacrine, donepezil, galantamine, memantine, and rivastigmine.34-38... 

Adverse reactions associated with memantine include constipation, confusion, dizziness, headache, coughing, and hypertension. These adverse effects are similar to those experienced with ChE inhibitors. Extra monitoring should be done if memantine is given concurrently with a ChE inhibitor. 

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... 

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