The hypothesis of this study is that up to 150 mg of sertraline and up to 3 mg of telenzepine will be safe, tolerable, and have the effect of suppressing appetite, when taken in combination daily by mouth by healthy, overweight, adult men and women.

In this study, up to 12 people will be assigned to one of 4 groups: A, B, C, and D, and will receive 0, 50, 100, or 150 mg of sertraline per day. People in Groups B, C, or D will receive an initial dose of 50 mg sertraline. People in Groups C and D will receive an additional 50 mg of sertraline per week.

Up to 10 people from each group who were able to tolerate their sertraline dose for at least 5 days will begin taking 50 mg of sertraline plus doses of telenzepine that will increase from 1 mg to 2 mg to 3 mg over a 7-day period (they will receive each combination). On the day before they begin taking this combination of drugs, their appetite will be evaluated (on a visual scale of 0 to 100) before and after 3 meals.

The appetites of each person, assessed by the visual scale, will be evaluated on the last day of the period (Day 7) before and after 3 meals of each combination treatment, while they are staying in the research unit. The amount of food they eat will be determined.

Based on safety and tolerability assessments of individuals, and of the previous groups who received lower doses of the combination of drug, a decision will be made whether to further increase the dose of these drugs.

Since the appetites of each person will be evaluated on the last day of the period (Day 7) before and after 3 meals of each combination treatment, people in this study will stay in the research unit for approximately 2½ days, starting on Day 6 of their previous treatment, so appetite evaluations can be made on Day 7 after a fixed meal in the evening of Day 6. These people will continue the stay in the research unit when they begin each telenzepine dose increase, so a 24 hour safety observation may be made immediately after the increase.

After the final doses of telenzepine have been received, people in Groups C and D will continue to receive sertraline 50 mg per day for an additional 7 days or until the study physician decides when sertraline should be discontinued. People will return to the study unit for final visit, 2 weeks after they have received their last sertraline dose.

Inclusion Criteria:

• In good health based on medical history, physical examination, ECG, routine laboratory tests, and BMI >/= 30 kg/m2 and </=30 40 kg/m^2.
• Males and females agree to use described birth control methods.
• Non-smoker.
• Willing and able to be confined to the clinical research facility.
• Willing and able to comply with the protocol and able to communicate with investigators.
• Able to comprehend and willing to provide written informed consent.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, or allergic disease (including drug allergies; patients with untreated, asymptomatic, seasonal allergies may be enrolled), surgical conditions, cancer or any other condition that might in the opinion of the investigator impair the ability of the subject to complete the study or significantly interfere with the absorption, distribution, metabolism, or excretion of the study drugs.
• Evidence or history of clinically significant psychiatric disease including major depression, mania, or hypomania, and history of suicide attempts or suicidal ideation. Subjects with a Beck Depression Inventory-II (BDI-II) score >13 at screening are excluded.
• Clinically relevant abnormal findings at the screening examination (including laboratory tests and ECG).
• Screening ECG which demonstrates at least one of the following: heart rate > 100 bpm, QRS > 120 msec, QTc > 450 msec, PR > 220 msec or any rhythm other than sinus rhythm, sinus bradycardia, or sinus arrhythmia.
• Change in weight > 5 kilograms within 3 months of screening.
• History of alcohol consumption exceeding 14 drinks/week (1 drink equaling 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of hard liquor) within the 6 months before study entry.
• Sitting systolic blood pressure ≤90 millimeters of mercury (mmHg) or ≥140 mmHg, diastolic blood pressure </= 50 mmHg or >/= 90 mmHg and judged to be clinically significant by the investigator.
• Positive result on drug screen, hepatitis B surface antigen (HBsAg), hepatitis C (HCV), or human immunodeficiency (HIV) tests.
• Use of prescription or non-prescription drugs, vitamins, or dietary supplements within 14 days prior to the first dose of study medication. Subjects on oral contraceptives and subjects who have used acetaminophen at doses of < 2 grams/day are eligible for study entry. Any exception to this must be felt not to impact the integrity of the data and must be jointly agreed upon by the investigator and medical monitor.
• Treatment with any investigational drug, use of any known CYP450 enzyme- inducing/inhibiting agents (e.g., barbiturates, phenothiazines, cimetidine, St. John's Wort) or herbal supplements within 30 days prior to the first dose of study medication.
• Treatment with any psychotropic medication within 90 days of screening.
• History of drug abuse or dependence within 180 days of screening.
• Febrile illness within 5 days prior to the first dose of study medication.
• Inadequate venous access.
• Known allergy to sertraline or telenzepine.
• History of an active eating disorder such as anorexia nervosa, bulimia or binge eating disorder.
• Elevated ALT (> 2X ULN) or total bilirubin (> 1.6 mg/dL)
• Have diabetes mellitus (fasting plasma glucose > 126 mg/dL)
• Have been on weight loss medications in the past 6 months