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Effects of fenamate on inhibitory postsynaptic currents in Purkinje's cells

A Yu Dvorzhak1

  • 1Department of Brain Studies, Institute of Neurology, Russian Academy of Medical Sciences, Moscow, Russia. a_dvorzhak@mail.ru

Bulletin of Experimental Biology and Medicine
|January 16, 2009
PubMed

Insights

Nonsteroidal anti-inflammatory drugs mefenamic and tolfenamic acids prolong inhibitory currents in mouse brain cells. These fenamate drugs also reduce the amplitude of these crucial neuronal signals.

Area of Science:

  • Neuropharmacology
  • Cellular Neuroscience
  • Drug Discovery

Background:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain and inflammation.
  • The fenamate group of NSAIDs, including mefenamic and tolfenamic acids, are known for their analgesic properties.
  • Understanding the precise cellular mechanisms of NSAIDs, particularly their effects on neuronal signaling, is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the effects of mefenamic acid and tolfenamic acid on spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in Purkinje cells.
  • To determine how these fenamate NSAIDs modulate the amplitude and duration of inhibitory neurotransmission in the cerebellum.

Main Methods:

  • Whole-cell patch-clamp recordings were performed on Purkinje cells in mouse cerebellar slices.
  • The study utilized concentrations of mefenamic and tolfenamic acids ranging from 3 to 30 microM.
  • Analysis focused on spontaneous miniature inhibitory postsynaptic currents (mIPSCs) to assess changes in neuronal excitability.

Main Results:

  • Both mefenamic acid and tolfenamic acid significantly prolonged the duration of miniature inhibitory postsynaptic currents.
  • A notable reduction in the amplitude of miniature inhibitory postsynaptic currents was observed with both drugs.
  • These effects were concentration-dependent within the tested range of 3-30 microM.

Conclusions:

  • Fenamate NSAIDs, specifically mefenamic and tolfenamic acids, directly impact inhibitory neurotransmission in Purkinje cells.
  • The observed prolongation and amplitude reduction of mIPSCs suggest a modulatory role of these drugs on GABAergic signaling.
  • These findings contribute to understanding the neuropharmacological actions of fenamate NSAIDs and their potential central nervous system effects.

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