This investigation has three objectives. 1 & 2 To assess the acute and subchronic safety, tolerance, and intravenous pharmacokinetics of multiple escalating dosages of a 3 PHENYL TROPANE, which is a dopamine transporter (DAT) blocker, in cocaine abusers. 3. To assess the DAT occupancy changes induced by this 3 PHENYL TROPANE at two doses determined as 30% and 60% of the maximum tolerated (or toxic) dose in mg/kg in large animal species such as dog or primate. DAT occupancy will be estimated using iodine 125, beta CIT (RTI-55) and SPECT imaging. This a single-center, non-randomized, multiple dose, open label, fixed order dose escalating sequential residential/day hospital design that will study an intravenous 3 PHENYL TROPANE in 12 human volunteers ages 18 to 45 years old. Subjects will be treated with four sequentially escalating intravenous doses of the selected 3 PHENYL TROPANE at the following once daily dosages: 15%, 30% 45%, 60% of the animal toxic dose. Each given dose will be administered for five successive days. Complete pharmacokinetic profiles will be obtained on days one and five with trough levels on the intervening days. Each five- day dosage session will be followed by a minimum of 10 half-lives for washout between dose escalations. The total duration of this study is approximately 12 weeks per subject. Six subjects who volunteer for optional SPECT scanning will be assessed for DAT occupancy at 30%, and 60% of toxic doses of this 3 PHENYL TROPANE. Safety measurements include physical examinations, vital signs (BP, HR, RR, temperature) and 12-lead ECGs, hematology/serum, chemistry/urinalyses, psychometric determinations of cognitive function and affective state (e.g. depression and anxiety). Safety data will be analyzed by tabulation of symptoms and adverse events. The dose optimization found in this study will determine dosing for the subsequent cocaine administration study.
