A comparison of the receptor binding affinities between typical and atypical antipsychotics. Typical antipsychotics primarily share antagonist activity at dopamine D2 receptors. In contrast, atypical antipsychotics generally have a high affinity for other types of receptors, such as serotonin receptors, and a comparatively lower affinity for dopamine D2 receptors.

Typical and Atypical Antipsychotic Affinity to Different Receptors

A major class of antischizophrenic drugs that share an antagonist activity at dopamine D2 receptors

University of Rochester

Kalamazoo College

Antipsychotics are a drug class used to treat psychosis and other related disorders, such as schizophrenia. There are two types of antipsychotics: first-generation or typical antipsychotics include drugs like haloperidol, and second-generation or atypical antipsychotics include drugs like risperidone. Common brand names include Haldol, Mellaril, Prolixin, and Thorazine.

Antipsychotics

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.

The Dopamine Hypothesis of Schizophrenia

Breedlove, S. & Watson, N. (2017). Behavioral neuroscience, eighth edition. Oxford University Press.

Behavioral Neuroscience 8th Edition

Typical Antipsychotics

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

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

Antipsychotics work by inhibiting the neurotransmitter dopamine to treat positive psychotic symptoms such as auditory and visual hallucinations, delusions, and paranoia.  

Antipsychotics Mechanism of Action 

Based on the patient's symptoms described in the case study, which class of psychotropic medication would a psychiatrist most likely consider as a primary treatment? Explain your reasoning.

Psychiatric Medication Application

All of the early antipsychotics were found to block postsynaptic dopamine receptors, particularly D2 receptors. From this, researchers proposed the dopamine hypothesis.


Origins of the Dopamine Hypothesis of Antipsychotics

The effective dose of these antipsychotic drugs can be predicted given its affinity of D2 receptors, which supports the dopamine hypothesis.

Antipsychotic Drug Affinity for D2 Receptors as Support of the Dopamine Hypothesis of Antipsychotics

One problem of the dopamine hypothesis is that there is no relation between how long it takes for the symptoms to diminish and how long it takes the drugs themselves to block dopamine receptors, which shows that the relation between dopamine and schizophrenia is more complex.

Another problem of the hypothesis is seen in a study by Alpert and Friedhoff in 1980, where some people with schizophrenia do not respond to dopamine antagonsits at all.

Problems with the Dopamine Hypothesis of Antipsychotics

Brisch, R., Saniotis, A., Wolf, R., Bielau, H., Bernstein, H. G., Steiner, J., Bogerts, B., Braun, K., Jankowski, Z., Kumaratilake, J., Henneberg, M., & Gos, T. (2014). The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Frontiers in psychiatry, 5, 47. https://doi.org/10.3389/fpsyt.2014.00047

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