Target Engagement of Terazosin in Healthy Adults

The study is a single center, 37-day, controlled pilot study to assess the target engagement of Terazosin (TZ) in a single cohort of 6 healthy adult participants (3 men and 3 women.) During the study participants will undergo PET/CT scans, 7-Tesla MRI scans, blood draws, and an optional lumbar puncture (LP.) Participants will have their baseline ATP levels measured (at 0mg TZ.) They will then take doses of TZ at 1mg and will increase their dose on a weekly basis by 1mg until they reach a total dose of 5mg. ATP levels will be assessed on study days 8 and 36. Participants interested in voluntarily donating a sample of cerebral spinal fluid will undergo an optional lumbar puncture on study day 37.

The purpose of the study is to gain a better understanding of the mechanisms in which TZ acts in the brain. TZ was recently discovered to increase energy levels (in the form of ATP molecules) in the brain by enhancing glycolysis. By using different brain imaging techniques, blood assays and cerebral spinal fluid assays, the study will attempt to: 1) quantify the rate of glycolysis in the brain at different dosages of TZ, 2) quantify ATP levels in the brain at different dosages of TZ, 3) quantify ATP levels in blood at different dosages of TZ, and 4) assess the brain permeability of TZ. It is hoped that knowledge gained from the study will help guide future clinical trials using TZ for the treatment of various neurodegenerative diseases such as Parkinson's Disease.

Inclusion criteria

• Healthy Men or women aged 60-90

Exclusion criteria

• History of stroke
• Ineligibility for MRI (e.g. soft tissue metallic implants, clips, cardiac pacemaker, cardiac defibrillator, internal pacing wires, metallic fragments, shrapnel, etc.)
• Current use of more than one of the following classes of medications: beta blockers, ace inhibitors, angiotensin receptor blockers, calcium channel blockers, or diuretics
• Use of any alpha blockers (terazosin, doxazosin, alfuzosin, prazosin, or tamsulosin) in the past year.
• Current use of the over-the-counter supplement yohimbe
• Orthostatic hypotension defined as symptomatic decrease in BP > 20mmHg systolic or > 10mmHg diastolic and HR increase < 20bpm on supine to sitting or standing.
• Alcohol and drug abuse
• Clinically significant traumatic brain injury
• History of Type I diabetes
• Uncontrolled Type II diabetes
• Other known medical or psychiatric comorbidity that in the investigator's opinion would compromise participation in the study or increase fall risk
• Use of investigational drugs within 30 days before screening
• History of hemodynamic instability
• For females: pregnancy or breastfeeding