Mechanism for the ability of 5-HT

1A
agonism to enhance cognitive function in subjects with schizophrenia. There is a strong
consensus for the upregulation of 5-HT
1A
receptors in the brains of subjects with schizophrenia. The augmented tonic stimulation of
postsynaptic 5-HT
1A
receptors, as a result of the increased number of these receptors, may be a reason for impaired cognitive
function in patients with schizophrenia. Activation of presynaptic 5-HT
1A
autoreceptors by low-dose 5-HT
1A
partial agonists, by
means of inhibition of 5-HT neuronal activity, would produce a greater degree of decrease in the stimulation of postsynaptic 5-
HT
1A
receptors in patients with schizophrenia compared with psychiatrically normal subjects. Thus, low-dose 5-HT
1A
agonists
improve memory function in patients with schizophrenia but not in normal subjects. 5-HT: 5-hydroxytryptamine. Redrawn from.
[92]





Atypical antipsychotics achieve a greater balance between the positive and negative effects of
D2 receptor blockade than older antipsychotics, which bind to the 5-HT2A receptors to a far
lesser degree.
1
5-HT2A blockade increases dopamine release.
Why does blockade of 5-HT2A reduce side effects?
1,2

Extra dopamine may partially reverse some of the D
2
blockade by the antipsychotic
Decrease in D
2
blockade in nigrostriatal and tuberoinfundibular pathways reduces EPS and prolactin secretion
Blockade of 5-HT2A receptors in the mesocortical pathways reduces negative symptoms
Conventional
(first generation)
2

Atypical
(second generation)
2


1. Casey. J Clin Psychiatry 2004; 65 Suppl 9: 25-28.
2. Leonard. Fundamentals of Psychopharmacology. 3rd ed, 2003.
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