Behavioral pharmacological properties of a novel cannabinoid 1',1'-dithiolane delta8-THC analog, AMG-3

Behav Pharmacol. 2005 Sep;16(5-6):499-510. doi: 10.1097/00008877-200509000-00024.

Abstract

Newly developed cannabinoids may hold the promise of the development of useful and safe drugs. This study aimed to investigate the behavioral effects of the novel 1',1'-dithiolane delta8-HC analogue AMG-3, a cannabinomimetic molecule with high affinity for CB1/CB2 receptors. This analog was chosen for its binding affinity to these receptors, which is higher than that reported for delta8-tetrahydrocannabinol (delta8-THC). Behavioral responses were assessed after the administration of AMG-3 (1, 2, 4, 8 mg/kg, i.p.) in the open field, on the bar test, on the hot plate and in the intracranial self-stimulation procedure. AMG-3 increased the reactivity time on the hot plate in a dose- and time-dependent manner, indicating a long-lasting analgesic effect (at least 24 h). The substance was found dose-dependently to decrease spontaneous motor activity and to induce catalepsy, particularly at the highest dose (8 mg/kg). AMG-3 did not affect the rewarding value of intracranial self-stimulation, except to increase the reward threshold at the highest dose (8 mg/kg). The effects of the highest dose of AMG-3 on spontaneous activity and on the self-stimulation paradigm were completely reversed by pre-treatment with the CB1 receptor antagonist AM-251. These findings indicate that the administration of AMG-3 to rats elicits a specific behavioral profile, most probably associated with the activation of CB1 receptors and without effects indicating abuse potential.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Binding, Competitive / drug effects
  • Cannabinoids / chemistry
  • Cannabinoids / pharmacology*
  • Catalepsy / chemically induced
  • Catalepsy / physiopathology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cyclohexanols / metabolism
  • Dose-Response Relationship, Drug
  • Male
  • Molecular Structure
  • Motor Activity / drug effects
  • Pain / physiopathology
  • Pain / prevention & control
  • Pain Measurement / methods
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / physiology
  • Time Factors
  • Tritium

Substances

  • Cannabinoids
  • Cyclohexanols
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Tritium
  • AM 251
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • AMG 3