Anti-inflammatory effects of cerebrocrast in a model of rat paw edema and on mononuclear THP-1 cells

Eur J Pharmacol. 2002 Apr 26;441(3):203-8. doi: 10.1016/s0014-2999(02)01262-1.

Abstract

Cerebrocrast (IOS 1.1212; 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid di(2-propoxyethyl) diester) is a novel derivative of 1,4-dihydropyridine, which does not antagonize Ca(2+) influx in neuronal tissues. Since several classical dihydropyridines possess anti-inflammatory properties, we first studied the effects of cerebrocrast in a model of rat paw edema induced by carrageenan. Cerebrocrast had a preventative effect in this model of inflammation, with maximal activity (32-45% inhibition) in the 0.1-0.25 mg kg(-1) range. It was ineffective when added after the injection of carrageenan. Subsequent in vitro experiments showed that cerebrocrast in the micromolar range inhibited secretion of interleukin-1 beta, interleukin-6 and neurotoxic products by cells of the human monocytic THP-1 line while failing to affect secretion of tumor necrosis factor (TNF-alpha). It also lacked any direct neuroprotective effect against toxic secretions from stimulated THP-1 cells. The data obtained suggest that cerebrocrast may be useful not only in various inflammatory disorders of peripheral tissues, but also in treating neurodegenerative diseases, where inflammatory mechanisms in general and microglial activation, in particular, are thought to play an important role.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Dihydropyridines / pharmacology*
  • Dihydropyridines / therapeutic use
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Edema / drug therapy*
  • Forelimb / drug effects
  • Forelimb / metabolism
  • Forelimb / pathology
  • Humans
  • Male
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Rats
  • Rats, Wistar
  • Tumor Cells, Cultured

Substances

  • Anti-Inflammatory Agents
  • Dihydropyridines
  • 2,6-dimethyl-3,5-bis(2'-propoxyethoxycarbonyl)-4-(2''-difluoromethoxyphenyl)-1,4-dihydropyridine