Effects of the 5-HT(6) receptor antagonist, SB-271046, in animal models for schizophrenia.

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Pouzet B, Didriksen M, Arnt J

Effects of the 5-HT(6) receptor antagonist, SB-271046, in animal models for schizophrenia.

Pharmacol Biochem Behav. 2002 Apr;71(4):635-43.

PubMed ID

11888555 [ View in PubMed

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Abstract

The 5-HT(6) receptor is targeted by several new antipsychotics such as clozapine, olanzapine, and sertindole. We studied the effect of SB-271046 [5-chloro-N-(4-methoxy-3-piperazin-1-yl-phenyl)-3-methyl-2-benzothiophenesulfonam ide], a specific 5-HT(6) receptor antagonist, in three models for the positive symptoms of schizophrenia---D-amphetamine-induced hyperactivity, and D-amphetamine- or phencyclidine (PCP)-disrupted prepulse inhibition (PPI). We also tested this compound in a model for the negative symptoms of schizophrenia, PCP-disrupted social interaction (SIT) in rats. Induction of side effects by this compound was evaluated by testing its potency to reduce spontaneous motility, and to induce catalepsy in rats. The effect of SB-271046 was compared to clozapine in all models tested. This study showed that SB-271046 had no beneficial effect in PCP-disrupted SIT. However, SB-271046 dose-dependently normalised D-amphetamine-disrupted PPI, but did not reverse PCP-disrupted PPI. In addition, SB-271046 did not antagonise D-amphetamine-induced hyperactivity. Thus, this specific 5-HT(6) receptor antagonist was associated with a clear positive outcome in only one model for the positive symptoms of schizophrenia, and had no beneficial effect in the model for negative symptoms. Consequently, it is clear that SB-271046 is not expected to have an antipsychotic efficacy, at least when given as monotherapy.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sertindole	5-hydroxytryptamine receptor 6	Protein	Humans	Yes	Antagonist	Details