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New insights into pharmacological profile of LASSBio-579, a multi-target N-phenylpiperazine derivative active on animal models of schizophrenia.
Neves, Gilda; Antonio, Camila B; Betti, Andresa H; Pranke, Mariana A; Fraga, Carlos A M; Barreiro, Eliezer J; Noël, François; Rates, Stela M K.
Afiliación
  • Neves G; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Behav Brain Res ; 237: 86-95, 2013 Jan 15.
Article en En | MEDLINE | ID: mdl-23000351
Previous behavioral and receptor binding studies on N-phenylpiperazine derivatives by our group indicated that LASSBio-579, LASSBio-580 and LASSBio-581 could be potential antipsychotic lead compounds. The present study identified LASSBio-579 as the most promising among the three compounds, since it was the only one that inhibited apomorphine-induced climbing (5 mg/kg p.o.) and apomorphine-induced hypothermia (15 mg/kg p.o.). Furthermore, LASSBio-579 (0.5 mg/kg p.o.) was effective in the ketamine-induced hyperlocomotion test and prevented the prepulse inhibition deficits induced by apomorphine, DOI and ketamine with different potencies (1 mg/kg, 0.5 mg/kg and 5 mg/kg p.o., respectively). LASSBio-579 also induced a motor impairment, catalepsy and a mild sedative effect but only at doses 3-120 times higher than those with antipsychotic-like effects. In addition, LASSBio-579 (0.5 and 1 mg/kg p.o.) reversed the catalepsy induced by WAY 100,635, corroborating its action on both dopaminergic and serotonergic neurotransmission and pointing to the contribution of 5-HT(1A) receptor activation to its pharmacological profile. Moreover, co-administration of sub-effective doses of LASSBio-579 with sub-effective doses of clozapine or haloperidol prevented the apomorphine-induced climbing without induction of catalepsy. In summary, our results characterize LASSBio-579 as a multi-target ligand active in pharmacological animal models of schizophrenia, confirming that this compound could be included in development programs aiming at a new drug for treating schizophrenia.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Piperazinas / Esquizofrenia / Antipsicóticos Idioma: En Revista: Behav Brain Res Año: 2013 Tipo del documento: Article País de afiliación: Brasil

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Piperazinas / Esquizofrenia / Antipsicóticos Idioma: En Revista: Behav Brain Res Año: 2013 Tipo del documento: Article País de afiliación: Brasil