Inhibition of glutamate release by fluspirilene in cerebrocortical nerve terminals (synaptosomes).

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Wang SJ

Inhibition of glutamate release by fluspirilene in cerebrocortical nerve terminals (synaptosomes).

Synapse. 2002 Apr;44(1):36-41.

PubMed ID

11842444 [ View in PubMed

]

Abstract

Fluspirilene, a neuroleptic drug which is used clinically to treat schizophrenic patients, is a dopamine D2 receptor antagonist. Besides its well-known actions on the dopamine receptors, fluspirilene also displays calcium channel-blocking activity. The aim of this study was to investigate the effect of fluspirilene on the 4-aminopyridine (4AP)-evoked glutamate release in the cerebrocortical nerve terminals (synaptosomes). Fluspirilene reduced 4AP-evoked glutamate release in a concentration-dependent manner. This inhibitory effect was associated with a decrease in the depolarization-evoked increase in the cytoplasmic free Ca2+ concentration ([Ca2+]C), which could be completely abolished by the Ca2+ channel blocker omega-CgTX GVIA. Furthermore, fluspirilene did not produce any effect on ionomycin-evoked glutamate release. These results suggest that fluspirilene inhibits glutamate release primarily by reducing presynaptic Ca2+ influx via N-type Ca2+ channels in rat cerebrocortical nerve terminals. This finding implies that presynaptic Ca2+ channel blockade concomitant with inhibition of glutamate release and possibly other neurotransmitters release may contribute to the antischizophrenic action of fluspirilene.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Fluspirilene	Dopamine D2 receptor	Protein	Humans	Yes	Antagonist	Details
Fluspirilene	Voltage-dependent calcium channel gamma-1 subunit	Protein	Humans	Unknown	Inhibitor	Details