Schizophrenia: from dopamine to glutamate and back

Curr Med Chem. 2004 Feb;11(3):267-77. doi: 10.2174/0929867043456034.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antipsychotic Agents / therapeutic use*
  • Aripiprazole
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine Agonists / metabolism
  • Dopamine Agonists / therapeutic use*
  • Dopamine Antagonists / therapeutic use
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Glutamic Acid / metabolism
  • Mice
  • Piperazines / therapeutic use
  • Piperidines / chemistry
  • Piperidines / therapeutic use
  • Quinolones / therapeutic use
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism


  • Antipsychotic Agents
  • Dopamine Agonists
  • Dopamine Antagonists
  • Excitatory Amino Acid Antagonists
  • Piperazines
  • Piperidines
  • Quinolones
  • OSU 6162
  • Glutamic Acid
  • Aripiprazole
  • preclamol
  • pridopidine
  • Dopamine