Addictive Substance: Tobacco
Overview of molecular structure of Nicotine
Nicotine is the main addictive molecule in tobacco. This ingredient is both addictive and beneficial. Nicotine and one of its main metabolites, Cotinine, display antidepressant properties. Many mood stabilizers share a common structural motif: tertiary Nitrogen atom(s). When Nitrogen is bound to three carbon atoms it is deemed tertiary, when bonded to four Carbons it is considered quaternary. When looking for other compounds that will compete with nicotine in the body, searching for molecules that contain a tertiary Nitrogen atom and a pyridine ring (C5H5N) is a good start.
When nicotine enters the body, it is processed to produce metabolites cotinine and nornicotine. Nornicotine is produced when the body strips nicotine of a methyl (CH3) group (from its tertiary Nitrogen). Here, nicotine is a methyl donor. Later, when trying to find alternatives to nicotine, we will look for methyl donors.
Molecular structures of smoking cessation drugs
- Varenicline, marketed as Champix and introduced into the market in 2006, is a prescription tablet that is used for smoking cessation.
- Bupropion (marketed as Zyban) is an antidepressant and weight loss medication that was observed to also reduce nicotine cravings. Bupropion was first approved by the FDA as a smoking cessation aid in 1997.
- Cytisine, first marketed in Bulgaria in 1964 for smoking cessation, is a natural product found in plants. Studies have confirmed that it reduces cravings and blocks nicotine effects.
Molecular structures of human metabolites that are structurally similar to nicotine
- Nicotinamide adenine dinucleotide (NAD+) - currently ongoing research to use NADH for smoking cessation.
- Nicotinamide mononucleotide (NMN) Research indicates that NMN can help repair lung damage caused by smoke and replenish NAD+ levels that are depleted by cigarette consumption.
- Nicotinamide Riboside (NR) is a form of vitamin B3 that is a precursor to nicotinamide adenine dinucleotide. Research suggests that nicotine depletes natural NAD+ levels in the body.
- Vitamin B3 isomers contain the pyridine ring found in nicotine
Molecular structures of human metabolites that can serve as methyl (CH3) donors
Here is a list of human metabolites that have a tertiary or quaternary Nitrogen that can donate methyl groups similar to nicotine. All of these metabolites are available in supplement form:
- Trimethylglycine (TMG) - methyl donor for multiple pathways
- Folate (5-methyltetrahydrofolate) - tertiary Nitrogen donates methyl group, smoking lowers circulating concentrations of folate,
- L-α-Glycerophosphorylcholine (alpha-GPC) - precursor to methyl donor TMG
- Creatine Tertiary Nitrogen donates methyl to give creatine metabolite guanidinoacetic acid