Beyond the dopamine receptor: novel therapeutic targets for treating schizophrenia.
All current drugs approved to treat schizophrenia appear to exert their antipsychotic effects through blocking the dopamine D2 receptor. Recent meta-analyses and comparative efficacy studies indicate marginal differences in efficacy of newer atypical antipsychotics and the older drugs, and little effects on negative and cognitive symptoms. This review integrates findings from postmortem, imaging, and drug-challenge studies to elucidate a corticolimbic "pathologic circuit" in schizophrenia that may be particularly relevant to the negative symptoms and cognitive impairments of schizophrenia. Potential sites for pharmacologic intervention targeting glutatatergic, GABAergic, and cholinergic neurotransmission to treat these symptoms of schizophrenia are discussed.
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA. joseph_coyle@hms.harvard.edu
Joseph T
JT
Coyle
Darrick
D
Balu
Michael
M
Benneyworth
Alo
A
Basu
Alexander
A
Roseman
D000818:Animals; D014150:Antipsychotic Agents / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011950:Receptors, Cholinergic / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*
D014150:Antipsychotic Agents; D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate