Some info on the mechanism of action of typical vs. atypical antipsychotics.

1. Early in the development of schizophrenia,
Actions of typical there is a decrease in DA transmission to
antipsychotics: the cortex leading to -ve symptoms.
Eventually, this causes disinhibition of the
Cortex
D2R antagonists mesolimbic pathway causing +ve symptoms.
with D1R action
glutaminergic
Typical antipsychotics only treat +ve symptoms mesocortical pathway
and have relatively severe side-effects. - DAergic
GABAergic
This pathway is increased in Schizophrenia
leading to +ve symptoms
Ventral Striatum mesolimbic pathway - DAergic Ventral tegmental area
Dorsal Striatum nigrostriatal pathway - DAergic Substantia nigra
Infundibulum tuberoinfundibular pathway - DAergic
HT
Treating Schizophrenia with typical antipsychotic means that all
three DAergic pathways are inhibited.
=> side effects: motor and lactation.

2. Actions of atypical antipsychotics:
Milder D R antagonists with additional actions
on 5-HT (antagonism), Glu and other neurotransmitters Cortex
mesocortical pathway
Resources: - DAergic
P.568 Carlson’s.
P.559 R&D
P.44f Neuropharm glutaminergic
handout 5-HT1A R enhances
P.4 Mental Illness II handout. DA in mesocortical system.
Handout: low DA in cortex
overcome by atypicals (p.46).
5-HT-2A antagonism reduces DAergic output in the mesolimbic system GABAergic
combined with the D2R antagonism to reduce +ve symptoms
Ventral Striatum mesolimbic pathway - DAergic Ventral tegmental area
different 5-HT2A R action
Dorsal Striatum nigrostriatal pathway - DAergic Substantia nigra
5-HT2A R inhibits DA release
5-HT-2A antagonists disinhibit DA release in
dorsal striatum reducing motor side-effects. Raphe
Infundibulum tuberoinfundibular pathway - DAergic
HT