17.6: Antiepileptic 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 action of glutamate is primarily mediated through ionotropic glutamate receptors. Two prominent types of these receptors are the N-methyl-ᴅ-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. These receptors play crucial roles in facilitating glutamate's excitatory effects.

Glutamate antagonists are a class of drugs that inhibit the activity of glutamate receptors, particularly NMDA and AMPA receptors. Doing so reduces the overall synaptic excitation in the brain, making them effective tools in managing epilepsy. These antagonists help control seizures by modulating the excessive neuronal activity characteristic of epileptic episodes.

Several commonly prescribed glutamate antagonists include:

1. Felbamate (Felbatol): Felbamate treats various seizure types, including generalized tonic-clonic, absence, myoclonic, and atonic seizures. Its broad-spectrum effectiveness makes it a valuable option in epilepsy management.

2. Perampanel (Fycompa): Perampanel is another glutamate antagonist employed in epilepsy therapy. It is beneficial in treating focal and generalized seizures, offering flexibility in tailoring treatment to the patient's needs.

3. Topiramate (Topamax): Topiramate is known for its efficacy in managing focal and generalized seizures, making it a versatile choice for epilepsy treatment.

These glutamate antagonists are typically administered orally, offering a convenient delivery route for patients. They are readily absorbed into the bloodstream, ensuring efficient bodily distribution.

While effective, these drugs may have side effects, such as insomnia, anorexia, nausea, skin rash, dizziness, weight loss, and blurred vision.

Glutamate is the primary excitatory neurotransmitter in the brain, essential for neuronal communication.

It plays a crucial role in synaptic transmission, neuronal excitability, and plasticity, vital for cognition, learning, and memory.

The actions of glutamate are mediated by ionotropic glutamate receptors, including N-methyl-ᴅ-aspartate or NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or AMPA receptors.

Glutamate antagonists inhibit the activity of glutamate receptors like NMDA and AMPA, reducing synaptic excitation. They effectively manage epileptic seizures.

One example of this drug class is used for generalized tonic-clonic, absence myoclonic, and atonic seizures. Perampanel and lamotrigine are prescribed for focal and generalized seizures.

These drugs are administered orally and are readily absorbed.

Potential side effects may include insomnia, nausea, skin rash, dizziness, and weight loss.