Clozapine's mechanisms of action: non-dopaminergic activity rather than anatomical selectivity.
The mechanisms of clozapine's unusual actions were investigated in anesthetized rats. Sensory field potentials were recorded in the nucleus accumbens, striatum and somatosensory cortex. Both haloperidol and clozapine suppressed responses in the striatum and accumbens. Clozapine's but not haloperidol's subcortical actions were unaffected by dopamine depletion. In addition, the cortical effects of the two drugs differed. These data indicate that clozapine has non-dopaminergic activity but no particular specificity for limbic basal ganglia structures. While it is known that clozapine acts as a serotonergic and cholinergic antagonist, several considerations suggest that action on still another transmitter system, possibly glutamate, needs to be investigated.
Lidsky
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TI
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, 10314.
Banerjee
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SP
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D003024:Clozapine; D006220:Haloperidol; D004298:Dopamine