Chlorpromazine is a typicsalphenothiazine antipsychotic drug, which block the dopamine D2 receptor that usedto treat schizophrenia.Ø Generally, inthe mesolimbic pathway of the brain, dopamine isreleased by the presynaptic neuron and binds to dopamine D2 receptors, which belong to the GPCR coupledto inhibitory G-protein (G?i). G?i ? inhibit AC ? inhibits cAMP ? inhibit PKAfrom being stimulated ? less Ca release (Tritsch et al., 2015).
The receptors on the postsynaptic neuronin schizophrenic brain, are too sensitive to its effect, resulting in an overreceptivity to dopamine. Chlorpromazine acts as an antagonist on dopaminereceptors, therefore, forbidding the over activity of dopamine, which leads tothe blocking of the positive symptoms of schizophrenia such as hallucinations, delusions anddisorganized speech. Nevertheless, there is little or no impact on the negativesymptoms of schizophrenia (Bernard et al.
, 2008).For the short term management of anxiety,agitation or disturbed behavior of psychiatric conditions, chlorpromazine antagonizestwo receptors: 5HT-2 receptor and H1 receptor.v Serotonin (5HT-2) ,serotonin binds to (5HT-2) receptors which areGPCR 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 CRFproduction, CRF then stimulates stress hormone release (ACTH), that consequence in anxiogenic effects (Ranabir, 2011). Chlorpromazine blocks theserotonin receptors, subsequently, lowering glutamate and stress hormonerelease, which results in reducing aggression, anxiety and disturbed behaviors(Ansah et al.
, 2011).v Histamine (H1) receptors, activation of H1 receptor lead tostimulation in most brain regions (such as thalamus, brain stem, and amygdala) overcoupled to Gq/11proteins, and then PIP2 issplit into IP3and DAG by PLC, IP3 releases Ca (Billington et al., 2003). Moreover, it result in direct block of K channel, Ca -dependent K channelscan be activated, leading to depolarization and thus ?neural excitation.
Chlorpromazine acts as histamine antagonist, subsequently, decrease histamine effects and k channels are no longer inhibitedand no neuronal excitation, which results in reducing aggression, anxiety anddisturbed behaviors (Sergeeva, 2009).