Bisnorcymserine in Healthy Adult Volunteers

• Age greater than or equal to 55 years.
• Mini Mental State Examination (MMSE) > 27 at screening and at Visit 2-Day 1.
• Women who are able to become pregnant must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) at screening and prior to study drug administration
• Both men who are able to father children and women of childbearing potential must be willing to use an adequate method of contraception (see section 7) to avoid conception throughout the study and for up to 30 days of study drug administration.
• Body mass index (BMI) of 18.5 to 34.0, inclusive, and a total body weight of > 50 kg (110 pounds).
• Participants should be in good general physical and mental health as determined by medical history, a baseline physical examination, vital signs, clinical laboratory tests and electrocardiogram (EKG). Participants may have common age-related disorders (such as hypertension, type II diabetes, dyslipidemia, hypothyroidism) as long as these disorders are under good control by diet or medications.
• Able to sign own consent

EXCLUSION CRITERIA:

• Any clinically significant medical and psychiatric condition (including asthma active within the last 10 years or COPD, and drug abuse and dependency).
• Subject has used any tobacco products in the past 3 months.
• A history of significant allergy to any drug or systemic allergic disease (e.g., urticaria, atopic dermatitis).
• Pregnant or lactating females.
• Subject with a positive urine test for drugs of abuse at screening or at admission to the clinic on study Day 1.
• Subject has consumed any alcohol within 48 hours prior to Visit 2; and cannot or is unwilling, thereafter to abstain from drinking alcohol for the remainder of the subject s study participation.
• Subject is positive for HIV, hepatitis B surface antigen or hepatitis C antibody tests at screening.

• Any clinically significant laboratory abnormality. These include:

  • CBC: WBC \< 3000 /mm\^3; Hb \< 12 g/dL; Liver function tests: ALT, AST, Bilirubin (total, direct, indirect), Alkaline Phosphatase > 1.5 x the upper normal limit of the laboratory
  • Serum Creatinine > 1.5 mg/dL; Serum Glucose >150mg/dL
  • Resting supine blood pressure outside of a systolic blood pressure range of 90-140 mmHg or a diastolic blood pressure outside a range of 50-90 mmHg on two consecutive measurements taken up to 10 minutes apart.Resting supine heart rate greater than 100 bpm or less than or equal to 55 55 bpm on two consecutive measurements taken up to 10 minutes apart.
  • Any clinically significant abnormality on screening 12-lead EKG (e.g., heart block, conduction disorders, ventricular and/or atrial arrhythmias).
• Routine or PRN consumption of the following herbal/dietary supplements are not permitted, if used within 2 weeks before the screening visit at doses higher than the recommended daily intake: Omega-3 fatty acids (> 1000 mg/day), Vitamin E (> 400IU/day). Ginkgo biloba, St. John's wort and ginseng are not permitted, if used at any dose within 2 weeks before the screening visit.

• Medications that are excluded are:

  • Insulin
  • Anti-parkinsonian medications (such as levodopa/carbidopa, amantadine, bromocriptine, pergolide, selegiline)
  • Typical or atypical neuroleptics
  • Narcotic analgesics at any dose within 4 weeks prior to screening.
  • Long-acting benzodiazepines or barbiturates (such as clonazepam, diazepam, phenobarbital) within 4 weeks prior to screening
  • Short-acting anxiolytics or sedative hypnotics more frequently than 2 times per week within 4 weeks prior to screening (sedative hypnotics should not be used within 102 hours of study drug administration)
  • Medications with known significant cholinergic or anticholinergic side effects (such as pyridostigmine, tricyclic antidepressants, meclizine, oxybutynin) within 4 weeks prior to screening
  • Anti-convulsants (such as phenytoin, Phenobarbital, carbamazepine) within 2 months prior to screening
  • Medications for Alzheimer s disease (such as donepezil or memantine)
  • Beta-Blockers
  • Corticosteroids (Systemic)
  • Neuromuscular-Blocking Agents (non-depolarizing)
  • Succinylcholine
  • Any other drug (including prescription, over the counter medications and supplements) that may pose a risk to the subject or produce overlapping side effects with the study medication. Participants will not be taken off of medications for the purpose of this study.
• Donation or loss of 400 mL or more of blood within 56 days prior to and subsequent to screening.
• Participation in another research study involving an investigational drug within 30 days or 5 half-lives, whichever is longer.
• Known allergy or hypersensitivity to the investigational study drug and to the microcrystalline cellulose used as placebo.