Chlorpromazine is a typicalphenothiazine antipsychotic drug, which act as antagonist to dopamine D2receptor that used to treat schizophrenia.Ø Normally, dopamine is released by thepresynaptic membrane in the mesolimbic pathway of the brain and binds to dopaminergic D2 receptors,which are the GPCR coupled to inhibitory G-protein, dopamine binding consequencesin dissociation of the G-protein to G?i. G?i ? inhibit AC ? inhibits cAMP ? inhibitPKA from being activated ? less Ca release (Tritsch et al.
, 2015). In schizophrenic brain, thereceptors on the postsynaptic membrane are too sensitive to its effect,resulting in an over receptivity to dopamine. Chlorpromazine acts as anantagonist on dopaminergic receptors, therefore, preventing the over activityof dopamine, which leads to the blocking of the positive symptoms of schizophrenia (e.g., delusions, hallucinations and disorganized speech) (Bernard et al.
, 2008). For the shortterm management of anxiety, agitation or disturbed behavior of psychiatricconditions, chlorpromazine antagonizes two receptors: 5HT-2 receptor and H1receptor.Ø Serotonin binds to (5HT-2) receptors which are GPCR coupled to Gq protein, then PIP2 is cleaved by PLC to DAG and IP3 (results in release of Ca)( Roth, 2015).Serotonin participates inmodulating glutamate release, stimulates stress hormone release and activates CRF,that consequence in anxiogenic effects(Ciranna, 2006). Chlorpromazine blocks theserotonin receptors, subsequently, lowering both glutamate and stress hormonerelease, which results in reducing aggression, anxiety and disturbed behaviors. Ø Histamine (H1) receptors, H1 receptors are coupled to Gq proteins, then PIP2 is cleaved by PLC to DAG and IP3 (results in release of Ca) (Billington et al., 2003).
H1 receptor caninhibit k channels in neurons, leading to depolarization and thus increasingneuronal excitation. Chlorpromazine acts as histamine antagonist, consequently,decrease histamine effects and k channels are no longer inhibited and noneuronal excitation, which results in reducing aggression, anxiety anddisturbed behaviors (Sergeeva,2009).