Study to investigate the safety, tolerability and pharmacokinetics of GSK598809 in otherwise healthy volunteers. This study is required because this drug is being developed for the treatment of nicotine dependence. It is important to evaluate how this drug interacts in healthy smokers. The study is planned to consist of a single part, with 4 dosing periods. Subjects will receive 3 escalating doses of GSK598809 and 1 dose of placebo. There will be at least 1 week of wash out between doses. In each dosing period 14 subjects will receive escalating doses and 4 subjects will receive placebo. The actual doses used will be determined based on the safety/ tolerability and pharmacokinetics during the previous dose. It is expected that the duration of this study will be approximately 10 weeks.

Inclusion:

• A healthy man or woman
• 18 - 50 years old
• Neither too fat, nor too thin
• Female subjects must use an acceptable method of contraception from the first dose of study medication until 90 days following the final follow-up visit.
• Female subjects must not be breast feeding and should not have been breast feeding for a month.
• Male subjects must agree to use an acceptable method of contraception from the first dose of study medication until 90 days following the final follow-up.
• Subjects need to smoke 20 - 40 cigarettes a day inclusive for at least the past year and to not have tried to quit in the 3 months before the start of the study.

Exclusion:

• Any current medical or psychiatric illness
• Any history of chronic medical or psychiatric illnesses
• Previous or current alcohol or drug abuse/dependence including nicotine
• Personal or family history of prolonged QTc syndrome