Safety, tolerability, and pharmacokinetics of repeated oral doses of 2-hydroxybenzylamine acetate in healthy volunteers: a double-blind, randomized, placebo-controlled clinical trial

BMC Pharmacol Toxicol. 2020 Jan 6;21(1):3. doi: 10.1186/s40360-020-0382-y.


Background: 2-Hydroxybenzylamine (2-HOBA) is a selective dicarbonyl electrophile scavenger being developed as a nutritional supplement to help protect against the development of conditions associated with dicarbonyl electrophile formation, such as the cognitive decline observed with Mild Cognitive Impairment or Alzheimer's disease.

Methods: This study evaluated the safety, tolerability, and pharmacokinetics of repeated oral doses of 2-HOBA acetate (500 or 750 mg) administered to healthy volunteers every eight hours for two weeks. The effects of 2-HOBA on cyclooxygenase function and cerebrospinal fluid penetrance of 2-HOBA were also investigated.

Results: Repeated oral administration of 2-HOBA was found to be safe and well-tolerated up to 750 mg TID for 15 days. 2-HOBA was absorbed within 2 h of administration, had a half-life of 2.10-3.27 h, and an accumulation ratio of 1.38-1.52. 2-HOBA did not interfere with cyclooxygenase function and was found to be present in cerebrospinal fluid 90 min after dosing.

Conclusions: Repeated oral administration of 2-HOBA was found to be safe and well-tolerated. These results support continued development of 2-HOBA as a nutritional supplement.

Trial registration: Studies are registered at (NCT03555682 Registered 13 June 2018, NCT03554096 Registered 12 June 18).

Keywords: Humans; Pharmacokinetics; Safety; Salicylamine; γ-Ketoaldehydes.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Benzylamines / adverse effects
  • Benzylamines / blood
  • Benzylamines / cerebrospinal fluid
  • Benzylamines / pharmacokinetics*
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Young Adult


  • Benzylamines
  • 2-(aminomethyl)phenol

Associated data