Memantine prevents MDMA-induced neurotoxicity
C Chipana1, J Camarasa, D Pubill
1Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Nucli Universitari de Pedralbes, Universitat de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
Neurotoxicology
|November 6, 2007
Summary
Memantine (MEM) prevents MDMA-induced neurotoxicity by blocking alpha-7 nicotinic acetylcholine receptors (nAChRs). This study shows MEM
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- MDMA (ecstasy) is an illicit drug known to cause long-term neurotoxicity.
- Previous research links MDMA to alpha-7 nicotinic acetylcholine receptors (nAChRs) and dopaminergic neurotoxicity.
- Alpha-7 nAChRs are implicated in neurodegenerative conditions like Alzheimer's disease.
Purpose of the Study:
- To investigate memantine's (MEM) efficacy in preventing MDMA-induced neurotoxicity in rats.
- To assess MEM's ability to counteract MDMA's oxidative effects in mice striatal synaptosomes.
- To explore the role of alpha-7 nAChR antagonism in MDMA neuroprotection.
Main Methods:
- In vitro study using isolated mouse striatal synaptosomes to measure reactive oxygen species (ROS) production.
- In vivo study using Dark Agouti rats to assess MDMA neurotoxicity markers, including hyperthermia and [(3)H]paroxetine binding.
- Memantine (MEM) was used as an alpha-7 nAChR antagonist, with PNU 282987 as a specific agonist control.
Main Results:
- MDMA-induced ROS production in synaptosomes was fully inhibited by MEM, an effect reversed by a selective alpha-7 nAChR agonist.
- MDMA caused persistent hyperthermia in rats, unaffected by MEM pre-treatment.
- MDMA significantly reduced serotonergic markers [(3)H]paroxetine binding in rat hippocampus, an effect fully prevented by MEM.
Conclusions:
- Memantine effectively prevents MDMA-induced serotonergic neurotoxicity in vivo, likely through alpha-7 nAChR blockade.
- MDMA's oxidative effects in vitro are mediated by alpha-7 nAChRs and are sensitive to memantine.
- The study suggests memantine's potential as a neuroprotective agent against MDMA toxicity, possibly via alpha-7 nAChR antagonism or indirect mechanisms involving acetylcholine release.
Related Concept Videos
01:14Antiepileptic Drugs: Glutamate Antagonists
Glutamate is a fundamental neurotransmitter in the central nervous system, playing a vital role in neuronal communication and various cognitive processes. Glutamate stands as the principal excitatory neurotransmitter in the brain. Its presence is crucial for the communication between neurons, underpinning essential processes such as synaptic transmission, neuronal excitability, and plasticity. These functions are vital for higher-order cognitive processes, including learning and memory. The...
01:21Drugs Affecting Neurotransmitter Release or Uptake
Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
01:29Drugs Affecting Neurotransmitter Synthesis
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase, which converts...
01:30Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function. They...
01:23Antidepressant Drugs: MAOIs and Other Agents
Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
01:26Neurochemical Transmission: Sites of Drug Action
Neurochemical transmission, the conduction of electrical impulses between neurons mediated by neurotransmitters, plays a vital role in various physiological processes. Autonomic drugs exert their effects by modulating neurotransmission within the autonomic nervous system. For instance, drugs such as hemicholinium block the precursor uptake necessary for synthesizing acetylcholine, an essential autonomic neurotransmitter. Following synthesis, neurotransmitters are stored in vesicles. Metyrosine...