Effects of flavor ingredient ethyl vanillin on nicotine pharmacokinetics and neurotransmitters release

Ethyl vanillin, a key flavoring agent in tobacco, but its impact on nicotine pharmacokinetics and neurotransmitters relearse remains poorly understood.

Nicotine-administeted Sprague-Dawley rats were injected with vehicle or 1.0 mg/kg ethyl vanillin. Nicotine and its metabolite in blood and brain were quantified using real-time microdialysis coupled with HPLC-MS/MS. Compared to the Nicotine-only group, which showed a C_max of 152.07 ng mL^-1 and an AUC_(0-300 min) of 14.64 μg min·mL^-1, co-administration with ethyl vanillin significantly elevated blood nicotine levels, increasing the C_max and AUC_(0-300 min) to 294.23 ng mL^-1 and 24.74 μg min·mL^-1, respectively. Molecular docking analysis revealed ethyl vanillin exhibits stronger binding affinity with cytochrome P4502A6 (CYP2A6) compared to nicotine. Additionally, ethyl vanillin had minimal impact on nicotine-induced dopamine and γ-aminobutyric acid release in the nucleus accumbens.

This study demonstrated that ethyl vanillin increassed nicotine concentration in rat blood but had minimal impact on neurotransmitter release or brain nicotine levels. Ethyl vanillin exhibits stronger binding affinity with CYP2A6 compared to nicotine. These findings offer new insights into the pharmacokinetic and neurobiological effects of ethyl vanillin in tobacco products.