Remoxipride, a new potential antipsychotic compound with selective antidopaminergic actions in the rat brain.

Article Details

Citation

Copy to clipboard

Ogren SO, Hall H, Kohler C, Magnusson O, Lindbom LO, Angeby K, Florvall L

Remoxipride, a new potential antipsychotic compound with selective antidopaminergic actions in the rat brain.

Eur J Pharmacol. 1984 Jul 20;102(3-4):459-74.

PubMed ID

6149133 [ View in PubMed

]

Abstract

The novel substituted benzamide, remoxipride, preferentially blocked apomorphine-induced hyperactivity with weak effects on stereotypies. The potency of remoxipride was about 50 times higher than that of sulpiride. Remoxipride caused a weak, atypical form of catalepsy and showed a high separation between the ED50 for blockade of apomorphine-induced hyperactivity and the ED50 for induction of catalepsy (ratio 24). Remoxipride was shown to be a selective dopamine D2 receptor antagonist since it displaced [3H]spiperone (IC50 = 1570 nM) but not [3H]flupentixol (IC50 greater than 100 000 nM) in rat striatum, and did not inhibit striatal DA-sensitive adenylate cyclase in vitro (IC50 greater than 100 000 nM). Remoxipride is a potent antagonist of D2 receptors showing a dose-dependent blockade of [3H]spiperone and [3H]n-propylnorapomorphine in vivo binding with a potency equal to that of chlorpromazine. In contrast to haloperidol, remoxipride caused a preferential blockade of in vivo [3H]spierone binding in the mesolimbic DA rich areas and the substantia nigra with much less effect in the striatum. In addition, remoxipride produced a preferential increase of DA utilization following synthesis inhibition in the olfactory tubercle. Only minor changes in NA and 5-HT metabolism were observed while HVA and DOPAC levels were markedly elevated. Taken together, these results indicate that remoxipride is a potent, selective D2 receptor blocking agent with a preferential action in mesolimbic and extrastriatal dopamine-containing neurons.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Flupentixol	Dopamine D2 receptor	Protein	Humans	Yes	Antagonist	Details