• Modeling Mechanism：

  L-5-Hydroxytryptophan (L-5-HTP), as a direct precursor of central serotonin (5-HT), bypasses the 5-HT synthesis defect caused by tryptophan hydroxylase 2 (TPH2) gene polymorphism in DBA/1 mice, directly converting it into 5-HT in the brain, thereby supplementing the level of central serotonergic neurotransmitters. L-5-Hydroxytryptophan reduces the incidence of post-ictal respiratory arrest (S-IRA) by enhancing the regulatory function of the brainstem respiratory center and inhibiting abnormally activated respiratory depression pathways after epileptic seizures, without altering seizure susceptibility.

• Related Products：

  L-5-Hydroxytryptophan (T1379)

• Modeling Method：

  Experimental Subject：

  Mice: DBA/1 mice (SUDEP susceptibility model), C57BL/6J mice (control); Grouping:
  - Primed group (Primed DBA/1): Acoustic stimulation for 3–4 consecutive days starting at 26–28 days postnatal, establishing stable S-IRA susceptibility (1 month old, 10–15 g);
  - Non-primed group (Non-primed DBA/1): No acoustic stimulation pre-treatment (2–3 months old, 13–22 g)

  Dosage and Administration Route：

  ① Epilepsy induction methods (two pathways):
  - Acoustic stimulation: 96 dB SPL electric bell stimulation (maximum 60 seconds) to induce auditory-evoked seizures (AGSz);
  - Chemical induction: Pentylenetetrazole (PTZ) 75 mg/kg intraperitoneal injection, inducing generalised tonic-clonic seizures;
  ② Pharmacological intervention:
  - Acute administration: L-5-HTP 100–150 mg/kg intraperitoneally, with seizure induction 1 hour post-administration;
  - Repeated dosing: L-5-HTP 50–200 mg/kg intraperitoneally, once daily for two consecutive days, with seizure induction one hour after the second dose;

  Dosing Frequency and Duration Model：

  Acute administration: Single dose
  Repeated dosing: Once daily for 2 consecutive days

• Validation：

  1. Behavioral Validation (Core Indicators): - S-IRA Incidence: In DBA/1 mice after acoustic stimulation, the S-IRA incidence was ≥60% in the control group, decreasing to ≤20% in the 125-150 mg/kg acute administration group (p<0.01); the S-IRA incidence was 85.7% in the PTZ-induced control group, decreasing to 16.7% in the 200 mg/kg repeated administration group (p<0.05); - Seizure Phenotype: Wild-running and clonic seizures were still observed, with only 55-60% of the high-dose group showing blocked tonic seizures, without affecting seizure susceptibility; 2. Molecular Indicators: - Brainstem TPH2 Protein: TPH2 expression in sensitized DBA/1 mice was 33.7% lower than in C57BL/6J mice (p<0.05), and 5-HT levels in the brain significantly increased after 5-HTP intervention; 3. Functional Indicators: - Respiratory/ECG Monitoring: plethysmography When S-IRA is displayed, the respiratory signal is flat, and the ECG recording of cardiac electrical activity continues for several minutes before terminating. This respiratory-heart rhythm abnormality can be reversed in the 5-HTP group.

*Precautions：

*References：Zhang H,et,al. 5-Hydroxytryptophan, a precursor for serotonin synthesis, reduces seizure-induced respiratory arrest. Epilepsia. 2016 Aug;57(8):1228-35.