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Tytuł oryginału: Differences in the effects of haloperidol and clozapine on brain serotonin and dopamine metabolism and on tests related to extrapyramidal funcitons in rats.
Autorzy: Haleem Darakhshan J., Batool Farhat, Khan Nadia H., Kamil Noor, Ali Obaid, Saify Zafar S., Haleem Mohammad A.
Źródło: Med. Sci. Monitor 2002: 8 (9) s.BR354-BR361, il., bibliogr. 51 poz.
Sygnatura GBL: 313,278

Hasła klasyfikacyjne GBL:
  • neurologia
  • psychiatria i psychologia
  • farmacja

    Typ dokumentu:
  • tytuł obcojęzyczny
  • praca doświadczalna

    Wskaźnik treści:
  • zwierzęta
  • szczury
  • płeć męska

    Streszczenie angielskie: Background: An important goal of current neuroleptic research is to develop antipsychotic compounds with a low incidence of extrapyramidal side effects (EPS). Clozapine, the first of the atypical antipsychotics to be proven effective in treatment-resistant schizophrenia, is reported to produce less EPS than typical neuroleptics, such as haloperidol. Material/methods: The present study compares the neurochemical profiles of clozapine and haloperidol in rats. Animals injected (i.p.) with haloperidol or clozapine were sacrificed 1h later to collect brain samples. Neurochemical estimations were carried out by HPLC-EC. Results: Administration of haloperidol at doses of 1.0, 2.5 and 5.0 mg/kg increased the concentration of homovanillic acid (HVA), a metabolite of dopamine (DA), in the stratum and rest of the brain. Clozapine-injected rats (2.5, 5.0 and 10.0 mg/kg) showed smaller increases in the striatum, but not in the rest of the brain. Dihydroxyphenylacetic acid (DOPAC), another DA metabolite not affected by haloperidol, increased in teh striatum and decreased in the rest of the brain of clozapine-injected rats. 5-Hydroxyindoleacetic acid, the predominant metabolite of serotonin, increased with haloperidol and dereased with clozapine. A high dose of haloperidol (5.0 mg/kg) increased DA and 5-HT, while and equivalent does of clozapine (10.0mg/kg) decreased levels in the rest of the brain. The effects of both drugs on the HVA/5-HIAA and DOPAC/5-HIAA ratios were also different. Conclusions: THe differing activites of the two drugs at DA and serotonin receptors implies an important role for serotonin in treatment-resistant schizophrenia and a lower incidence of EPS.

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