β-Nicotyrine is a pyrolysis product of nicotine that can bind to cytochrome P450 (CYP) isoforms CYP2A6 and CYP2A13, and more effectively inhibit the activity of CYP2A6[1-2]. By inhibiting CYP2A subtypes, β-Nicotyrine is able to suppress DNA strand breaks induced by genotoxic tobacco metabolites[3-4].
In vitro, β-Nicotyrine (5–50μM) and Tobacco Nitrosamine (NNK; 100μM) were co-administered to metabolically active human hepatocyte cell line HepaRG for 12 hours, significantly inhibiting DNA single-strand and double-strand breaks induced by NNK bioactivation[5].
In vivo, β-Nicotyrine (0.05–1.0mg/kg) and nicotine (0.0125–0.2mg/kg) were co-administered subcutaneously to Sprague-Dawley rats that had undergone nicotine discrimination training, with testing conducted at 10- and 60-minute pretreatment intervals. This treatment significantly enhanced and prolonged the discriminative stimulus effects of nicotine[6].
References:
[1] Kramlinger VM, von Weymarn LB, Murphy SE. Inhibition and inactivation of cytochrome P450 2A6 and cytochrome P450 2A13 by menthofuran, β-nicotyrine and menthol. Chem Biol Interact. 2012 May 30;197(2-3):87-92.
[2] Denton TT, Zhang X, Cashman JR. Nicotine-related alkaloids and metabolites as inhibitors of human cytochrome P-450 2A6. Biochem Pharmacol. 2004 Feb 15;67(4):751-6.
[3] Shigenaga MK, Kim BH, Caldera-Munoz P, et al. Liver and lung microsomal metabolism of the tobacco alkaloid beta-nicotyrine. Chem Res Toxicol. 1989 Sep-Oct;2(5):282-7.
[4] Kurgat C, Kibet J, Cheplogoi P. Molecular modeling of major tobacco alkaloids in mainstream cigarette smoke. Chem Cent J. 2016 Jul 15;10:43.
[5] Ordonez P, Sierra AB, Camacho OM, et al. Nicotine, cotinine, and β-nicotyrine inhibit NNK-induced DNA-strand break in the hepatic cell line HepaRG. Toxicol In Vitro. 2014 Jul 15:S0887-2333(14)00135-0.
[6] Smethells JR, Wilde S, Muelken P, et al. β-Nicotyrine and e-cigarette abuse liability I: Pharmacodynamics and interaction with pharmacokinetics and discriminative stimulus effects of nicotine in rats. Drug Alcohol Depend. 2025 Dec 1;277:112949.
β-Nicotyrine是一种尼古丁的热解产物，可与细胞色素P450 (CYP) isoforms CYP2A6和CYP2A13结合，并能更有效地抑制CYP2A6的活性[1-2]。β-Nicotyrine通过抑制CYP2A亚型，β-Nicotyrine能够抑制由基因毒性烟草代谢物诱导的DNA链断裂[3-4]。
在体外，β-Nicotyrine(5–50μM)与Tobacco Nitrosamine(NNK；100μM)共同处理代谢活性的人源肝细胞系HepaRG 12小时，能够显著抑制由NNK生物活化所诱导的DNA单链和双链断裂[5]。
在体内，β-Nicotyrine(0.05–1.0mg/kg)与尼古丁(0.0125–0.2mg/kg) 联合皮下注射，用于处理已建立尼古丁辨别训练的Sprague-Dawley大鼠10分钟或60分钟，能够显著增强和延长尼古丁的辨别刺激效应[6]。