Disease Information

General Information of the Disease (ID: DIS00570)

• Name: Epilepsy
• ICD: ICD-11: 8A60

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 6 drug(s) in total

Idebenone

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Glutathione synthetase (GSH) [1]

• Sensitive Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Sensitive Drug: Idebenone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: Ellman assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: IDB had successful control over drug resistance in the rotenone corneal kindled model by bypassing blocked complex I. IDB has a good safety profile and can be considered an adjuvant along with standard antiseizure drugs in drug-resistant patients.

Key Molecule: Quinone reductase 1 (NQO1) [1]

• Sensitive Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Sensitive Drug: Idebenone
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Nrf2 signaling pathway; Activation; hsa05208
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: ELISA assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: IDB had successful control over drug resistance in the rotenone corneal kindled model by bypassing blocked complex I. IDB has a good safety profile and can be considered an adjuvant along with standard antiseizure drugs in drug-resistant patients.

Lamotrigine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Glutathione synthetase (GSH) [1]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Resistant Drug: Lamotrigine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: Ellman assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Key Molecule: Quinone reductase 1 (NQO1) [1]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Resistant Drug: Lamotrigine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Nrf2 signaling pathway; Inhibition; hsa05208
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: ELISA assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Levetiracetam

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Glutathione synthetase (GSH) [1]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Resistant Drug: Levetiracetam
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: Ellman assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Key Molecule: Quinone reductase 1 (NQO1) [1]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Resistant Drug: Levetiracetam
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Nrf2 signaling pathway; Inhibition; hsa05208
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: ELISA assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Phenytoin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Glutathione synthetase (GSH) [1]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Resistant Drug: Phenytoin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: Ellman assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Key Molecule: Quinone reductase 1 (NQO1) [1]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Resistant Drug: Phenytoin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Nrf2 signaling pathway; Inhibition; hsa05208
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: ELISA assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Pregabalin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Glutathione synthetase (GSH) [1]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Resistant Drug: Pregabalin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: Ellman assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Key Molecule: Quinone reductase 1 (NQO1) [1]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Resistant Drug: Pregabalin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Nrf2 signaling pathway; Inhibition; hsa05208
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: ELISA assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Valproic acid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Glutathione synthetase (GSH) [1]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Resistant Drug: Valproic acid
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: Ellman assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Key Molecule: Quinone reductase 1 (NQO1) [1]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Resistant Drug: Valproic acid
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Nrf2 signaling pathway; Inhibition; hsa05208
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: ELISA assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

References

• Ref 1: Attenuation of mitochondrial refractory epilepsy in rotenone corneal kindling model of drug resistance by idebenone: An approach to bypass mitochondrial complex I. Epilepsy Res. 2024 Nov;207:107458.