HU-211, a nonpsychotropic cannabinoid, produces short- and long-term neuroprotection after optic nerve axotomy

J Neurotrauma. 1996 Jan;13(1):49-57. doi: 10.1089/neu.1996.13.49.

Abstract

HU-211 is a novel synthetic analog of tetrahydrocannabinol that was recently shown in animal models to be nonpsychotropic. In this study we show that HU-211 can potentially be used as a neuroprotective compound in the CNS. Using a calibrated crush injury of adult rat optic nerve, we show that HU-211 can reduce injury-induced metabolic and electrophysiological deficits. Energy metabolism was monitored by measuring the intramitochondrial nicotine-amine adenine dinucleotide redox state hourly for 6 h after injury and treatment. Electrophysiological activity was assessed by compound action potential and visual evoked potential response. Beneficial effects were dose-dependent, being optimal at 7 mg/kg, administered intraperitoneally. The time window during which treatment was effective was found to be from the time of injury for at least 5 h, with treatment most effective at the time of injury. These results strongly suggest that HU-211, given immediately after CNS injury at the optimal dosage, may possess neuroprotective activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Axons
  • Brain Injuries / physiopathology*
  • Dose-Response Relationship, Drug
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology
  • Drug Administration Schedule
  • Electrophysiology / methods
  • Energy Metabolism / drug effects
  • Evoked Potentials, Visual / drug effects
  • Male
  • NAD / metabolism
  • Nerve Crush*
  • Neuroprotective Agents / pharmacology*
  • Optic Nerve / physiology*
  • Optic Nerve Injuries
  • Oxidation-Reduction
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Neuroprotective Agents
  • NAD
  • Dronabinol
  • HU 211