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Noncompetitive N-methyl-D-aspartate antagonists affect multiple ionic currents.

S Rothman1

  • 1Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.

The Journal of Pharmacology and Experimental Therapeutics
|July 1, 1988
PubMed
Summary
This summary is machine-generated.

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Ketamine, phencyclidine, and MK-801 block N-methyl-D-aspartate receptors and voltage-gated potassium channels in neurons. These drugs also affect sodium currents, but high concentrations suggest limited behavioral relevance for channel blockade.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Ketamine, phencyclidine (PCP), and MK-801 are known N-methyl-D-aspartate (NMDA) receptor antagonists.
  • Their precise mechanisms of action, particularly regarding behavioral and metabolic effects, require further elucidation.

Purpose of the Study:

  • To investigate the effects of phencyclidine, ketamine, and MK-801 on voltage-gated ion channels in cultured rat hippocampal neurons.
  • To determine if these drugs interact with potassium and sodium channels beyond their known NMDA receptor antagonism.

Main Methods:

  • Electrophysiological recordings (voltage clamp and current clamp) were performed on cultured rat hippocampal neurons.
  • The effects of phencyclidine, ketamine, and MK-801 on potassium and sodium currents were assessed.
  • The impact of these drugs on NMDA receptor-mediated currents was also evaluated.

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Main Results:

  • Phencyclidine, ketamine, and MK-801 reduced both early and steady-state potassium currents.
  • Phencyclidine and MK-801 affected action potential properties, indicating potential antagonism of sodium currents.
  • A slowly developing blockade of NMDA currents by phencyclidine and MK-801 was observed, even at hyperpolarized potentials.

Conclusions:

  • Ketamine, phencyclidine, and MK-801 interact with voltage-gated potassium and sodium channels.
  • While these drugs affect ion channels, the high concentrations needed suggest these interactions may not be behaviorally significant.
  • The findings expand the understanding of the complex pharmacology of these dissociative anesthetics.