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Schizophrenia: from dopamine to glutamate and back
M L Carlsson1, A Carlsson, M Nilsson
1Institute of Clinical Neuroscience, Neuropsychiatric Research Unit, Göteborg University, Sweden. maria.carlsson@psychiat.gu.se
Current Medicinal Chemistry
|February 18, 2004
Summary
Dopamine stabilizers, including partial dopamine receptor antagonists like OSU6162, show promise for treating schizophrenia symptoms. Research explored their efficacy in both clinical trials and a hypoglutamatergia mouse model.
Area of Science:
- Neuroscience
- Psychopharmacology
- Medicinal Chemistry
Background:
- Dopamine stabilizers have evolved from early partial agonists to antagonists.
- OSU6162, a phenylpiperidine-based dopamine stabilizer, demonstrated clinical efficacy.
- Schizophrenia's cognitive symptoms are linked to hypoglutamatergia.
Purpose of the Study:
- To review the development of dopamine stabilizers.
- To evaluate OSU6162's clinical potential.
- To test antipsychotics and a dopamine stabilizer in a schizophrenia mouse model.
Main Methods:
- Review of historical and recent dopamine stabilizer research.
- Clinical trial data analysis for OSU6162.
- Pharmacological testing in a hypoglutamatergia mouse model.
Main Results:
- OSU6162 exhibited antidyskinetic and antipsychotic effects in preliminary trials.
- Testing included traditional neuroleptics, 5-HT2/D2 antagonists, and partial dopamine receptor antagonists.
- Dopamine stabilizers were assessed for efficacy in a mouse model of cognitive deficits.
Conclusions:
- Dopamine stabilizers, particularly partial dopamine receptor antagonists, represent a significant therapeutic avenue.
- OSU6162 shows potential for treating schizophrenia.
- Further research in animal models is crucial for understanding treatment mechanisms.