Direct effect of neuroleptics on glutamate release.
In studies designed to assess the pre-synaptic effects of neuroleptics in vitro, synaptosomes were prepared from several regions of rat brain. These preparations were incubated in the presence of a representative of each of the major classes of neuroleptic--chlorpromazine, haloperidol, or clozapine, or with (+) or (-)butaclamol. The calcium-specific release of endogenous glutamic acid was reduced only in synaptosomes derived from the amygdala. In this area, each of these agents [except (-)butaclamol] reduced the release of glutamic acid to a maximum of 40% in a concentration-dependent manner. When [3H]glutamine was included in the incubation media, a reduction in the released [3H]glutamate was present with 10(-8) M haloperidol, and 5 X 10(-8) M (+)butaclamol, clozapine, or chlorpromazine. (-)Butaclamol was inactive at 10(-5) M, a concentration producing complete blockade of the release of [3H]glutamic acid when active agents were included. Again, the effects were observed only in the amygdala. All agents, including (-)butaclamol blocked the uptake of [3H]glutamine into depolarized synaptosomes.
D000679:Amygdala / Q000502:physiology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D002069:Butaclamol / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002746:Chlorpromazine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism* / Q000494:pharmacology; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism
D014150:Antipsychotic Agents; D005971:Glutamates; D005973:Glutamine; C011829:glutamic acid diethyl ester; D018698:Glutamic Acid; D001285:Atropine; D002069:Butaclamol; D003024:Clozapine; D006220:Haloperidol; D002118:Calcium; D002746:Chlorpromazine