Chlorpromazine is a typicalphenothiazine antipsychotic drug, which block the dopamine D2 receptor and serotonin 5HT-2 receptor that used to treat schizophrenia.Ø Generally, dopamineis released by the presynaptic neuron in the mesolimbic pathway of the brain and binds to dopamine D2 receptors, which are GPCR coupled toinhibitory G-protein (G?i). G?i ? inhibit AC ? inhibits cAMP ? inhibit PKA frombeing 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).Ø Serotonin (5HT-2), serotonin binds to (5HT-2) receptors which areGPCR coupled to Gq/11 proteinsand it has a regulatory role inglutamate pathway by activating PLC, which cleaved PIP2 into to DAG and IP3(results in release of Ca) (Roth, 2015).Inschizophrenic brain, the serotonin-mediated control of glutamate transmission in hippocampus isdisrupted due to hyperactivity of serotonin receptors(Ciranna, 2006). Chlorpromazineantagonize the serotonin receptors, consequently, there is no activation of PLCand thus ? the intracellular concentration of Ca (Ansah et al.
, 2011).For the short term management of anxiety,agitation or disturbed behavior of psychiatric conditions, chlorpromazineantagonizes two 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 inmodulating glutamate release(Ciranna, 2006).Moreover, it mediatethe neurogenic activation of CRF production, 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 is split into IP3andDAG by PLC, IP3 releases Ca (Billington et al., 2003). Moreover, it result in direct block of K channel, leading todepolarization and thus ?neural excitation.
Chlorpromazine acts as histamine antagonist, subsequently ?histamine effects, k channels are no longer inhibited, and thereis no neuronal excitation, which results in reducing aggression, anxiety anddisturbed behaviors (Sergeeva, 2009).