Nicotine, the principal alkaloid in tobacco, is considered to be a drug of abuse and has diverse pharmacological actions that are not completely understood. Nicotine, its metabolites, and related tobacco compounds are implicated as causative agents in diseases which are statistically more prevalent among smokers than non-smokers, e.g. lung cancer, respiratory and cardiovascular disorders, decreased fetal size and increased fetal complications. The metabolism of nicotine and related compounds is complex, and leads to the production of many metabolites. We have developed sensitive and specific assays to monitor levels of these compounds in physiological fluids, tissue extracts and in enzymatic and chemical experiments designed to determine the factors that influence the formation and catabolism of individual compounds. Specific and sensitive radioimmunoassays are available for nicotine, cotinine, Gamma(3-pyridyl)-Gamma-oxo-N-methylbutyramide, N-nitrosonornicotine, the NMN, NAD and NADP analogs of nicotine and cotinine, and N'-acylnornicotine analogs. By studying the action of these compounds in in vitro and in vivo systems, their activities can be assessed and the causes and consequences of adverse reactions better understood. Certain commonly used drugs inhibit nicotine to cotinine conversion in an in vitro system. These results suggest that special attention be given to concomitant intake of drugs when studying nicotine metabolism in man. Comparative epidemiological studies on specific populations may also reveal differences in metabolic patterns. The determination of cotinine levels in serum, urine or saliva samples is a reliable biochemical indicator of tobacco intake and is being used to validate the oral testimony given by subjects in smoking cessation programs. Emphasis is being placed on making these immunoassays more sensitive so that they can be used to obtain information about nicotine intake as a result of passive smoking. Non-radioactive immunoassays for nicotine and its metabolites will also be developed.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA002507-06
Application #
3207383
Study Section
(DABB)
Project Start
1985-01-01
Project End
1988-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Brandeis University
Department
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Cinciripini, P M; Lapitsky, L; Seay, S et al. (1995) The effects of smoking schedules on cessation outcome: can we improve on common methods of gradual and abrupt nicotine withdrawal? J Consult Clin Psychol 63:388-99
Cinciripini, P M; Lapitsky, L; Seay, S et al. (1995) A placebo-controlled evaluation of the effects of buspirone on smoking cessation: differences between high- and low-anxiety smokers. J Clin Psychopharmacol 15:182-91
Cinciripini, P M; Lapitsky, L G; Wallfisch, A et al. (1994) An evaluation of a multicomponent treatment program involving scheduled smoking and relapse prevention procedures: initial findings. Addict Behav 19:13-22
Thompson, S G; Barlow, R D; Wald, N J et al. (1990) How should urinary cotinine concentrations be adjusted for urinary creatinine concentration? Clin Chim Acta 187:289-95
Cinciripini, P M; Van Vunakis, H; Nezami, E et al. (1989) Nicotine regulation among heavy and light smokers in a non-stressful environment. Biol Psychol 28:251-64
van Vunakis, H; Tashkin, D P; Rigas, B et al. (1989) Relative sensitivity and specificity of salivary and serum cotinine in identifying tobacco-smoking status of self-reported nonsmokers and smokers of tobacco and/or marijuana. Arch Environ Health 44:53-8
Cinciripini, P M; Benedict, C E; Van Vunakis, H et al. (1989) The effects of smoking on the mood, cardiovascular and adrenergic reactivity of heavy and light smokers in a non-stressful environment. Biol Psychol 29:273-89
Van Vunakis, H; Tashkin, D P; Simmons, M et al. (1988) Decreased serum cotinine levels in smokers of both tobacco and marijuana as compared with smokers of tobacco only. Pharmacol Biochem Behav 30:895-8
Gritz, E R; Ippoliti, A; Jarvik, M E et al. (1988) The effect of nicotine on the delay of gastric emptying. Aliment Pharmacol Ther 2:173-8
Levine, L; Fujiki, H; Sakai, S et al. (1988) A radioimmunoassay for the teleocidins using 26 (2'-aminoethylthio)-tetrahydroteleocidin A-2 as hapten. Carcinogenesis 9:1629-33

Showing the most recent 10 out of 16 publications