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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