Highlights
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More effective treatments are needed for drug–resistant epilepsy
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Dapagliflozin, a potent SGLT2 inhibitor used for diabetes, may have anti-seizure effects
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Rats with PTZ–induced seizures had abatement of seizure activity when exposed to dapagliflozin
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The potential role of dapagliflozin as an antiepileptic drug should be further explored
Background
Epidemiology of drug-resistant epilepsy
Intracerebral transport of glucose
Attenuating seizure activity via inhibition of SGLTs
Methods
Ethics oversight
Study subjects and location
Drugs and dosing
Randomization and blinding
Experiment involving EEG measurement
Experiment involving behavioral measurement
Statistical analysis
Results
EEG spike wave percentage
Arm | Seizure onset (seconds) | Duration of single seizures (seconds) | Duration of high frequency or high amplitude spiking (seconds) | Total seizure duration (seconds) |
---|---|---|---|---|
A1 | 0 ± 0.0 | 0 ± 0.0 | 0 ± 0.0 | 0 ± 0.0 |
A2 | 45.08 ± 9.3 | 10.2 ± 3.10 | 5.3 ± 0.93 | 2564.2 ± 105.6 |
A3 | 110.3 ± 16.8** | 6.06 ± 1.08* | 3.2 ± 0.85* | 685.2 ± 60.8** |
A4 | 185.7 ± 12.1** | 2.1 ± 0.93* | 0.8 ± 0.12* | 451.8 ± 35.9** |
Arm | Intervention | Recovery time (seconds) |
---|---|---|
A1 | Saline control arm | 0 ± 0.0 |
A2 | PTZ at 70 mg/kg and saline | 565.8 ± 12.7 |
A3 | PTZ at 70 mg/kg and dapaglifozin at 75 mg/kg | 483.3 ± 35.2* |
A4 | PTZ at 70 mg/kg and dapaglifozin at 150 mg/kg | 368 ± 24.9* |
Racine’s stages scores
Arm | Intervention | Racine’s | TFMJ (s) | p–value |
---|---|---|---|---|
B1 | NS (control arm) | 0 ± 0.0 | Not reached | – |
B2 | NS, PTZ 70 mg/kg | 5.5 ± 0.2 | 68.3 ± 3.4 s | – |
B3 | NS, PTZ 70 mg/kg, DGF 75 mg/kg | 2.33 ± 0.5 | 196.7 ± 23.0 s | p < 0.0001 |
B4 | NS, PTZ 70 mg/kg, DGF 150 mg/kg | 2.1 ± 0.5 | 268.3 ± 23.1 s | p < 0.0001 |