Role of Metabolites in Nicotine Dependence (2) - 5

Previous studies have shown that cotinine, a metabolite of nicotine, antagonizes some of the
effects of nicotine. One study showed that nicotine eliminates some of the beneficial
effects of the nicotine patch in reducing withdrawal symptoms. The purpose of this study was
to examine the effects of cotinine. The results generally showed no effects on
self-administration of cigarettes, although higher serum nicotine levels were observed on
the highest doses of cotinine compared to placebo or lower doses of cotinine.

Inclusion Criteria:

Male/Female subjects ages 21-45 yrs. inclusive, with a smoking history of at least 1 pack
of cigarettes daily for at least 1 year. Subject must be in good health as verified by
medical history, screening examination, and screening laboratory tests. Subject must
provide written informed consent to participate in the study and be motivated to stop
smoking for a short term.

Exclusion Criteria:

History of myocardial infarction, angina pectoris, sustained or episodic cardiac
arrhythmias, symptomatic peripheral vascular disease, peptic ulcer disease or any other
medical condition which the physician or investigator deems inappropriate for
participation. Insulin-dependent diabetes. Pregnant or lactating, or not using adequate
birth control methods. Requirement of any form of regular psychotropic medication
(antidepressants, antipsychotics, or anxiolytics) and recent psychiatric history). Chronic
use of systemic steroids or antihistamines. Skin sensitivity which would preclude use of a
transdermal system. Abuse of alcohol or any other recreational or prescription drug. Use
of any other tobacco products including smokeless tobacco and nicotine products. Previous
use of transdermal nicotine system. Inability to fulfill all scheduled visits and
examination procedures throughout the study period.