Anti-glutamatergic effects of clozapine

Neurosci Lett. 1993 Dec 12;163(2):155-8. doi: 10.1016/0304-3940(93)90370-z.

Abstract

Clozapine (Cz) is unique in its efficacy with treatment refractory patients and its freedom from motor side effects. The present work shows that Cz, even after dopamine depletion, suppresses responses evoked via the monosynaptic glutamatergic corticostriatal pathway. In addition, Cz is effective in displacing [3H]MK-801 from striatal homogenates. These data indicate that Cz is a glutamate antagonist. It is unclear, however, if this pharmacological action could explain Cz's lack of motor effects and it's antipsychotic potency.

MeSH terms

  • Animals
  • Binding, Competitive
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology*
  • Clozapine / pharmacology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dizocilpine Maleate / metabolism
  • Dizocilpine Maleate / pharmacology
  • Dopamine / metabolism*
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists
  • Glutamates / physiology*
  • Glutamic Acid
  • Haloperidol / pharmacology
  • Humans
  • Membrane Potentials / drug effects
  • Rats
  • Vibrissae / innervation

Substances

  • Excitatory Amino Acid Antagonists
  • Glutamates
  • Glutamic Acid
  • Dizocilpine Maleate
  • Clozapine
  • Haloperidol
  • Dopamine