The focus of our technology is the development of drug products that block nicotine’s actions on the brain and in the body to treat smoking-related illness in smokers.
Nicotine is normally not present in the body. Rather, it is absorbed from tobacco during smoking (or using smokeless tobacco--snuff, chewing tobacco) or from using electronic cigarettes (vaping) in which flavored, vaporized solutions containing nicotine are inhaled. Nicotine is also absorbed by the body when using Nicotine Replacment Therapy (NRT) smoking cessation products: nicotine-containing gum, patches, and inhalers.
Nicotine binds to receptors found in the brain and other organs, producing many types of physiological effects, including:
- increase in heart rate and blood pressure, vasoconstriction
- feelings of pleasure, improved mood, and diminished anxiety
- development of a strong addiction to nicotine
Nicotine addiction drives smokers to continue smoking and is the reason why it is difficult for many to quit. Long-term nicotine exposure leads to increased risk of developing impaired respiratory function (such as emphysema, chronic obstructive pulmonary disease or exacerbation of asthma) in smokers due to the direct irritating action of smoke on the lungs. Also, increased rates of cancer of the lung and elsewhere are attributed to the carcinogens produced by the combustion of tobacco.
Additional major adverse cardiovascular consequences of chronic exposure to nicotine from smoking include increased occurrence of:
- atherosclerosis
- myocardial infarction
- stroke
- exacerbation of peripheral arterial disease (PAD)
- death due to cardiovascular disease
In a patient with PAD, the narrowing and decreased flexibility of blood vessels throughout the body due to atherosclerosis accompanied by nicotine-induced vasoconstriction results in diminished blood flow and less oxygen availability to tissues. Clinical symptoms include decreased ability to walk due to moderate to severe pain, large skin ulcers that often do not heal, and impaired recovery from injury or surgery.
FDA approved treatments to combat nicotine’s addictiveness are:
- Nicotine Replacement Therapy (NRT) marketed as lozenges, gums, patches
- bupropion (Zyban®)
- varenicline (Chantix®)
These medications produce a very modest level of sustained smoking abstinence. Randomized controlled clinical trials of these anti-smoking drugs (along with behavioral “quit”-counseling) typically show a 1-year smoking abstinence rate of 5% to 15% of patients above the 5% to 10% success rate seen in placebo-treated control subjects receiving behavioral counseling alone.1-3
Improved treatments to block the addictive effects of nicotine and block its direct adverse effects on the cardiovascular system and other organs are needed. None of the existing anti-smoking products block nicotine’s action at all nicotine receptors throughout the body.
- Cahill, K., Stevens, S., Perera, R. & Lancaster, T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database of Systematic Reviews, doi:10.1002/14651858.CD009329.pub2 (2013).
- Fiore MC, J. e. C., Baker TB, et al. Treating tobacco use and dependence: 2008 update. (ed HHS) (Public Health Service, Rockville, MD, 2008).
- Gonzales, D. et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 296, 47-55 (2006).
