Distribution of Prominent GPCR Families with Known Endogenous Ligands in the Central Nervous System
Receptor Type
Receptor Family mGluRs
Subtype
Endogenous Ligands
GABA
mGluRl Glutamate mGluR5
mGluR2
mGluR3
mGluR4
mGluR6
mGluR7
mGluR8
GABA-B GABA
Cerebral Spinal Basal
Amygdala Cortex Hippocampus Hypothalamus Cord Ganglia
Other
Ref.
60-65
Retina
a Based on published rat and human mRNA distribution. b Includes autoradiography data.
Cloning of first dopamine receptor clozapine chlorpromazine haloperidol typical neuroleptics
S2/D2 atypicals aripiprazole
1950
imipramine iproniazid
1960 Valium 1970
1980 1990
fluoxetine
2000
2010
1o TCA's
2o TCA's
MAOI's benzodiazepines
Cloning of first serotonin receptor
FIGURE 7.1 History of psychiatric drug development. Timeline shows emergence of selected drug mechanisms (solid arrows) and therapeutic agents (plain text) with relevance to schizophrenia (above the line) and depression/anxiety (below the line). S2/D2 = serotonin 5HT2A + dopamine D2 receptor antagonists. TCA = tricyclic antidepressants. MAOI = monoamine oxidase inhibitor. SSRI = selective serotonin reuptake inhibitor. SNRI = selective serotonin and norepinephrine reuptake inhibitor.
effects. Human genetics studies are beginning to define susceptibility genes for schizophrenic disorders,73 and molecular pharmacology approaches to development of more selective compounds may provide the next wave of breakthroughs in disease understanding and treatment.
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