Typical Antipsychotic are separated into 1st Generation and 2nd Generation.

1st Generation Antipsychotics include:  
- Chlorpromazine

- Mesoridazine 

- Perphenazine 

- Thioridazine 

- Trifluoperazine 

- Butyrophenone 

- Haloperidol 

- Others:  Loxapine, Molindone, Thiothixene 


Rutgers University

Scripps College

A class of drugs that typically alleviate symptoms of schizophrenia. (Also called neuroleptics)

- The Dopamine Hypothesis

- Typical Antipsychotics

- Long-Term Effects of Antipsychotic Drugs

- Atypical Antipsychotics

- The Glutamate Hypothesis

Antipsychotic Drugs

https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/schizophrenia-guide.pdf

Treating Schizophrenia

National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 5452, Thioridazine. Retrieved October 21, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/Thioridazine.

Thioridazine (Mellaril)

National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 4078, Mesoridazine. Retrieved October 21, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/Mesoridazine.

Mesoridazine (Serentil)

National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 2726, Chlorpromazine. Retrieved October 21, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/Chlorpromazine.

Chlorpromazine (Ormazine, Thorazine, or Largactil)

National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 5566, Trifluoperazine. Retrieved October 21, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/Trifluoperazine.

Trifluoperazine (Stelazine)

National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 4748, Perphenazine. Retrieved October 21, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/Perphenazine.

Perphenazine (Trilafon)

National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 3559, Haloperidol. Retrieved October 21, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/Haloperidol.

Haloperidol (Haldol)

Hypothesis: Schizophrenia results from an underactivation of glutamate receptors.

- Origin of Hypothesis

The Glutamate Hypothesis of Antipsychotics

While the discovery of antipsychotic drugs helped with the treatment of schizophrenia, there were quite significant side effects.

- Dyskinesia
- Tardive Dyskinesia
- Supersensitivity psychosis
- Involuntary movements of the arms, legs, tongue and facial muscles, resulting in Parkinson’s-like tremors

Long-Term Effects of Antipsychotic Drugs

These are a class of antipsychotic drugs that have a high affinity for other types of receptors and not dopamine receptors. They are also known as 2nd Generation Antipsychotics. They can be prescribed for Schizophrenia and other types of severe thought disorders. They can target dopamine and serotonin receptors to treat schizophrenia's negative symptoms, such as withdrawal and apathy; newer drugs may treat both positive and negative symptoms.

Atypical Antipsychotics include: 
- Aripiprazole (Abilify)

- Clozapine (Clozaril)

- Olanzapine (Zyprexa)

- Quetiapine (Seroquel)

- Risperidone (Risperdal)

- Ziprasidone (Geodon)

Atypical Antipsychotics

Typical Antipsychotics

Both typical and atypical antipsychotics appear to inhibit the release of pro-inflammatory cytokines and potentially promote regular neurogenesis in schizophrenia patients by decreasing oxidative stress. Studies of prenatal administration of some antipsychotics in mice models have demonstrated a decrease in psychosis-like behaviors in the offspring. Given that the microglial inflammatory mechanisms are particularly pronounced in schizophrenia, this is a particular area of interest for future pharmacological research.

Effects of Antipsychotics on Microglia

The dopamine hypothesis posits that schizophrenia is linked to irregularities in the dopamine system. The original theory suggested that the disorder was caused by a general excess of dopamine or an overabundance of dopamine receptors. However, this view has been refined. More recent research indicates that dopamine abnormalities are specific to different brain regions. An oversupply of dopamine in the limbic system is thought to be responsible for positive symptoms like hallucinations and delusions, while a deficit of dopamine in the prefrontal cortex is associated with negative symptoms such as avolition and alogia.

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