Aripiprazole, a novel antipsychotic drug, inhibits quinpirole-evoked GTPase activity but does not up-regulate dopamine D2 receptor following repeated treatment in the rat striatum.

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Inoue A, Miki S, Seto M, Kikuchi T, Morita S, Ueda H, Misu Y, Nakata Y

Aripiprazole, a novel antipsychotic drug, inhibits quinpirole-evoked GTPase activity but does not up-regulate dopamine D2 receptor following repeated treatment in the rat striatum.

Eur J Pharmacol. 1997 Feb 19;321(1):105-11.

PubMed ID

9083792 [ View in PubMed

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Abstract

Aripiprazole, a quinolinone derivative, is a new dopaminergic agent which has been recently developed and demonstrated to be clinically useful as an antipsychotic drug with reduced extrapyramidal motor side effects. Here, we found that aripiprazole competed [3H]spiperone binding with a 100-fold higher affinity than [3H]SCH23390 binding, and inhibited the quinpirole-induced facilitation of high-affinity GTPase activity in rat striatal membranes. The effects of chronic administration of aripiprazole and haloperidol on dopamine D2 receptor binding and mRNA level in rat striata were examined by a [3H]spiperone binding assay and a ribonuclease protection assay. Haloperidol induced a significant rise in Bmax of [3H]spiperone binding at 1 mg/kg and in the level of dopamine D2L receptor mRNA at 4 mg/kg. A high dose of aripiprazole (100 mg/kg) only tended to increase the Bmax of [3H]spiperone binding non-significantly, and had no effect on the level of dopamine D2L receptor mRNA. These results indicated that aripiprazole had an antagonistic activity to dopamine D2 receptors with a high affinity, but that the potency of aripiprazole to up-regulate dopamine D2 receptors in the striatum was much smaller than that of haloperidol. This small up-regulation may be related to the ability to aripiprazole to act without side effects including tardive dyskinesia.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Aripiprazole	Dopamine D2 receptor	Protein	Humans	Yes	Antagonist Partial agonist	Details
Aripiprazole lauroxil	Dopamine D2 receptor	Protein	Humans	Yes	Partial agonist	Details