BACKGROUND: Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats. OBJECTIVE: To investigate the neuroprotective effects of flunarizine (FNZ), lamotrigine (LTG) and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats. DESIGN AND SETTING: This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People’s Hospital, Guangdong Medical College. MATERIALS: Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ + LTG, and model groups, with 10 rats in each group. METHODS: Rats in the FNZ, LTG, and FNZ + LTG groups received intragastric injections of FNZ (0.5 mg/kg/d), LTG (10 mg/kg/d), and FNZ (0.5 mg/kg/d) + LTG (10 mg/kg/d), respectively. Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia. Rats in the model group were not administered any drugs. Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, following birth. MAIN OUTCOME MEASURES: Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method. RESULTS: Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ + LTG groups following ischemia, compared with the model group (P < 0.01). However, these values were significantly greater in the FNZ and LTG groups, compared with the FNZ + LTG group, following ischemia (P < 0.01). CONCLUSION: Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior. BACKGROUND: Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats. OBJECTIVE: To investigate the neuroprotective effects of flunarizine FNZ), lamotrigine (LTG) and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats. DESIGN AND SETTING: This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People’s Hospital, Guangdong Medical College MATERIALS: Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ + LTG, and model groups, with 10 rats in each group. METHODS: Rats in the FNZ, LTG , and FNZ + LTG groups received intragastric injections of FNZ at 0.5 mg / kg / d, LTG at 10 mg / kg / d, and FNZ at 0.5 mg / kg / d + , respectively. Drugs w Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, the following birth. MAIN OUTCOME MEASURES: Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method. RESULTS: Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly high erin the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ + LTG groups The following ischemia, compared with the model group (P <0.01). However, these values ​​were significantly greater in the FNZ and LTG groups, compared with the FNZ + LTG group, following ischemia (P <0.01). CONCLUSION: Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior.