An initial animal proof-of-concept study for central administration of clozapine to schizophrenia patients
| Autor: | Daniel J. Abrams, Jun J. Yang, Nasser H. Zawia, Karen E. Stevens, Wei Wei, Kevin S. Choo, Lijun Zheng, Thomas J. Anchordoquy |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Reflex Startle Psychosis Elevated plus maze Side effect Cell Survival medicine.drug_class Chemistry Pharmaceutical Atypical antipsychotic Beta-Cyclodextrins In Vitro Techniques Pharmacology Hippocampus Article Rats Sprague-Dawley Mice Route of administration medicine Animals Humans Maze Learning Clozapine Cells Cultured Biological Psychiatry Injections Intraventricular Behavior Animal beta-Cyclodextrins medicine.disease 2-Hydroxypropyl-beta-cyclodextrin Rats Disease Models Animal Psychiatry and Mental health Acoustic Stimulation Mice Inbred DBA Schizophrenia Drug Design Anesthesia Evoked Potentials Auditory Exploratory Behavior Neurotoxicity Syndromes Schizophrenic Psychology Psychology Antipsychotic Agents medicine.drug |
| Zdroj: | Schizophrenia Research. 100:86-96 |
| ISSN: | 0920-9964 |
| DOI: | 10.1016/j.schres.2007.10.012 |
| Popis: | While clozapine is the acknowledged superior pharmacotherapeutic for the treatment of schizophrenia, the side effect profile, which includes potentially fatal complications, limits its usefulness. Central administration of clozapine directly into the brain could circumvent many of the side effect issues due to the dramatic reduction in dose and the limitation of the drug primarily to the CNS. The present study demonstrates that clozapine can be formulated as a stable solution at physiological pH, which does not have in vitro neurotoxic effects at concentrations which may be effective at treating symptoms. Acute central administration improved auditory gating deficits in a mouse model of schizophrenia-like deficits. Assessment of behavioral alterations in rats receiving chronic central infusions of clozapine via osmotic minipump were performed with the open field and elevated plus mazes. Neither paradigm revealed any detrimental effects of the infusion. While these data represent only an initial investigation, they none-the-less suggest that central administration of clozapine may be a viable alternate therapeutic approach for schizophrenia patients which may be effective in symptom reduction without causing behavioral or neurotoxic effects. |
| Databáze: | OpenAIRE |
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