An Open Label Phase I/II Study of Dopamine Transporter Receptor Occupancy With OROS and Immediate Release Methylphenidate as Measured With C-11 Altropane in Human Subjects
An Open Label Phase I/II Study of Dopamine Transporter Receptor Occupancy With OROS and Immediate Release Methylphenidate as Measured With C-11 Altropane in Human Subjects
The specific aim of this study is to document the pharmacokinetics of DAT receptor occupancy
 of OROS and immediate release (IR) MPH using PET scanning with C-11 altropane as the ligand.
 We hypothesize that the time to maximal receptor occupancy and the degree of receptor
 occupancy of immediate release (IR) MPH will be shorter and greater (respectively) than with
 an equipotent dose of OROS MPH.
This protocol seeks to document the pharmacokinetics of DAT receptor occupancy of OROS and
 immediate release (IR) MPH using PET and C-11 altropane. The main target of MPH in the brain
 is the dopamine transporter (DAT). We have an exquisitely sensitive methodology to measure
 DAT occupancy using C-11 Altropane and Positron Emission Tomography (PET). This research will
 provide novel and unique information toward a better understanding of the mechanism of action
 of long-acting stimulant formulations to enable new drug development and an estimation of the
 relative abuse potential of the current formulation.
Inclusion Criteria:

 1. Signed written informed consent to participate in the study.

 2. Age: 18 - 55

 3. If female, non-pregnant, non-nursing with a negative serum pregnancy test and using an
 adequate form of birth control.

 4. Supine and standing blood pressure within the range 110/60 to 150/90 mmHg.

 5. Heart rate, after resting for 5 minutes, within the range 46-90 beats/min.

 6. Subjects who are within 20% of the ideal weight for height as

 7. Right handed.

 Exclusion Criteria:

 1. Diagnosis of any psychotic disorder, bipolar disorder, severe depression, severe
 anxiety, or Autism. Subjects with mild mood, oppositional, conduct, and anxiety
 disorders may be permitted to participate if considered appropriate by the
 investigator.

 2. Scores of Baseline Scales:

 Hamilton Depression Scale > 17 (out of a possible 67 on the 21-item scale)[18] Beck
 Depression Inventory > 19 (out of a possible 63 on the 21-item scale)[19] Hamilton
 Anxiety Scale > 21 (out of a possible 56 on the 14-item scale) [20]

 3. Tics or Tourette's Syndrome.

 4. History of head trauma with loss of consciousness, organic brain disorders, seizures,
 or neurosurgical intervention.

 5. Any clinically significant chronic medical condition, in the judgment of the
 investigator.

 6. Mental impairment as evidenced by an I.Q. <75.

 7. Exposure to dopamine receptor antagonists within the previous three (3) months.

 8. Exposure to radiopharmaceuticals within four (4) weeks prior to PET scan.

 9. Subjects receiving psychotropic medication.

 10. Any clinically significant abnormality in the screening laboratory tests, vital signs,
 or 11-lead ECG, outside of normal limits.

 12. Any woman of childbearing potential who is seeking to become pregnant or suspects that
 she may be pregnant.

 13. Subjects with a known recent history (within the past six (6) months) of illicit drug
 or alcohol dependence