Highly potent activity of (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol in animal models of Parkinson's disease

J Med Chem. 2011 Jun 9;54(11):3866-74. doi: 10.1021/jm2001579. Epub 2011 May 13.

Abstract

(1R,2R,6S)-3-Methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 possesses potent antiparkinsonian activity in both MPTP and haloperidol animal models. The use of compound 1 resulted in nearly full recovery of the locomotor and exploratory activities and was as effective as the comparator agent (levodopa). All eight stereoisomers of compound 1 have been synthesized and the influence of the absolute configuration on the antiparkinsonian activity of compound 1 was shown.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Antiparkinson Agents / chemical synthesis*
  • Antiparkinson Agents / chemistry
  • Antiparkinson Agents / pharmacology*
  • Cyclohexanols / chemical synthesis*
  • Cyclohexanols / chemistry
  • Cyclohexanols / pharmacology*
  • Disease Models, Animal
  • Dopamine Antagonists / pharmacology
  • Drug Synergism
  • Haloperidol
  • Levodopa / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Conformation
  • Motor Activity / drug effects*
  • Neurotoxins / pharmacology
  • Parkinson Disease / drug therapy*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy*
  • Rats
  • Rats, Wistar
  • Receptors, Neurotransmitter / metabolism
  • Stereoisomerism

Substances

  • 3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol
  • Antiparkinson Agents
  • Cyclohexanols
  • Dopamine Antagonists
  • Neurotoxins
  • Receptors, Neurotransmitter
  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Haloperidol