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Clozapine is an antipsychotic drug used in the treatment of schizophrenia. Schizophrenia is a mental disease characterized by symptoms like strong emotions, unusual thinking, and loss of interest in life. Clozapine has proven to be more effective than other antipsychotic drugs in the treatment of schizophrenia. It lowers the risk of committing suicide, tardive dyskinesia, decreased relapse, and improvement of cognition. P-glycoprotein helps in transporting drugs and also determines the uptake and efflux of a series of drugs. This process affects their plasma and tissue concentrations of drugs in the plasma and tissues and eventually their final effects. It functions as a transmembrane efflux pump. It pumps substrates from inside to outside of the cell

Clozapine is a second-generation antipsychotics drug. Clozapine acts as an antagonist to dopamine and serotonin receptors. Clozapine is P-glycoprotein substrates since it binds with a higher affinity to dopamine D4 than the dopamine D2 receptor thus contributing to the reduction in negative symptoms and extrapyramidal symptoms. Clozapine is a partial 5-HT1A agonist, contributing to the reduction of negative symptoms and extrapyramidal symptoms, and a muscarinic M1, M2, M3, M5, histamine, and alpha-1 adrenergic-receptor antagonist. Metabolite of clozapine (Norclozapine) actively works on the M1 and M4 receptors. Clozapine is metabolized to norclozapine and other metabolites by the Cytochrome P450 enzymes metabolizes Clozapine to norclozapine. Clozapine has a short The plasma half-life of Clozapine drug is short ranging 12 to 16 hours.

Risperidone just like Clozapine is an antipsychotic drug that is used in the treatment of mental disorders such as schizophrenia, autism, and Bipolar I disorder. Both of the drugs can be used in combination therapy. Clozapine is administered orally while risperidone is administered both orally and through injection. Risperidone is also a P-glycoprotein substrate as it binds to dopamine receptors, serotonin receptors, histamine H1 receptors, and adrenergic receptors.

9-OH risperidone Table Diagram







SEM/SD Cbrain/Cplasma SEM/SD Cbrain SEM/SD



SEM/SD Cbrain/Cplasma SEM/SD



80 7.2 305 21 0.26 0.12 745 66 230 13 3.23 1.44
Doran et al 2005
Kirschbaum et al 2008 30 70 120 30 0.25 0.11 280 70 130 19 2.15 0.96

Wang et al


24 15 329 149 0.072 0.03 706 248 351 205 2.01 0.90
Brzozowska et al 2017 20 2 110 10 0.18 0.08 470 40 120 15 3.91 1.75
Pacchioni et al 2009
Holthoewer et al 2010 12 8 102 3 0.11 0.05 11 9 160 20 0.068 0.03

In the experiment, risperidone was established to be very stable under physiological conditions and low pH. Also, it is established their release can be easily be controlled based on various parameters such as drug load.

In the 9-OH Risperidone Table Diagram, the brain to plasma ratio in Knock out type mice is higher than the in Wild Type. The Knock out type does not express anything.

The concentration of drugs in the plasma is high than in the brain in both the wild type and knocked out mice. The plasma contains both bound and unbound drug molecules. The bound drug molecules are bounded to plasma proteins. The unbound drug molecule moves in the brain cell passing through the brain-blood barrier to be in equilibrium.

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