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Schizophrenia: From Dopamine to Glutamate and Back

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The first part of the present review describes the exciting journey of dopamine stabilizers, starting in the early eighties with the development of the partial dopamine agonist (-)-3-PPP of phenylpiperidine structure, via various compounds with aminotetraline structure with preferential autoreceptor antagonist properties, and then back again to phenylpiperidine compounds carrying substituents on the aromatic ring that transformed them from partial dopamine agonists to partial dopamine receptor antagonists, such as OSU6162. OSU6162 was brought to the clinic and has in preliminary trials showed antidyskinetic and antipsychotic efficacy. The second part of this review describes results from a hypoglutamatergia mouse model for cognitive symptoms of schizophrenia, where we have tested traditional neuroleptics, new generation antipsychotics with marked 5-HT2 vs dopamine D2 receptor blockade as well as a dopamine stabilizer belonging to the partial dopamine receptor antagonist category.
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Keywords: cognition; dopamine stabilizer; glutamate; mk-801; mouse; schizophrenia; video tracking

Document Type: Review Article

Affiliations: Goteborg University, Institute of Clinical Neuroscience, Neuropsychiatric Research Unit, Guldhedsgatan 19, SE-413 46 Goteborg, Sweden.

Publication date: 2004-02-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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