Chlorpromazine  is a typicsal
phenothiazine antipsychotic drug, which block the dopamine D2 receptor that used
to treat schizophrenia.

Ø  Generally, in
the mesolimbic pathway of the brain, dopamine is
released by the presynaptic neuron and binds to dopamine D2 receptors, which belong to the GPCR coupled
to inhibitory G-protein (G?i). G?i ? inhibit AC ? inhibits cAMP ? inhibit PKA
from being stimulated ? less Ca release (Tritsch et al., 2015). The receptors on the postsynaptic neuron
in schizophrenic brain, are too sensitive to its effect, resulting in an over
receptivity to dopamine. Chlorpromazine acts as an antagonist on dopamine
receptors, therefore, forbidding the over activity of dopamine, which leads to
the blocking of the positive symptoms of schizophrenia such as hallucinations, delusions and
disorganized speech. Nevertheless, there is little or no impact on the negative
symptoms of schizophrenia (Bernard et al., 2008).

For the short term management of anxiety,
agitation or disturbed behavior of psychiatric conditions, chlorpromazine antagonizes
two receptors: 5HT-2 receptor and H1 receptor.

v  Serotonin (5HT-2) ,serotonin binds to (5HT-2) receptors which are
GPCR coupled to Gq/11 proteins, then PIP2 is cleaved by PLC to DAG and IP3
(results in release of Ca) and then mediate excitatory neurotransmission ( Roth,
 2015).Serotonin participates in modulating glutamate release(Ciranna,
2006).Moreover, it  mediate the neurogenic activation of CRF
production, CRF then stimulates stress hormone release (ACTH), that consequence in anxiogenic effects (Ranabir, 2011). Chlorpromazine blocks the
serotonin receptors, subsequently, lowering glutamate and stress hormone
release, which results in reducing aggression, anxiety and disturbed behaviors
(Ansah et al., 2011).

v   Histamine (H1) receptors, activation of H1 receptor lead to
stimulation in most brain regions (such as thalamus, brain stem, and amygdala) over
coupled to Gq/11proteins, and then PIP2 is
split into IP3and DAG by PLC, IP3 releases Ca (Billington et al., 2003). Moreover, it result in direct block of K channel, Ca -dependent K channels
can be activated, leading to depolarization and thus ?neural excitation. Chlorpromazine acts as histamine antagonist, subsequently, decrease histamine effects and k channels are no longer inhibited
and no neuronal excitation, which results in reducing aggression, anxiety and
disturbed behaviors (Sergeeva, 2009).