Anti-glutamatergic effects of clozapine.
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.
Lidsky
T I
TI
NYS Institute for Basic Research, Staten Island, NY 10314.
Yablonsky-Alter
E
E
Zuck
L
L
Banerjee
S P
SP
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D014738:Vibrissae / Q000294:innervation
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D003024:Clozapine; D006220:Haloperidol; D004298:Dopamine