Antipsychotic Medications: Choosing Based on Receptor Binding Profile

Antipsychotic medications exert their “antipsychotic” activity via antagonism at the D2-subtype dopamine receptor but also have action at a variety other neurotransmitter receptors. These receptor actions dictate both clinical and adverse effects and may be used to guide drug selection for an individual patient or describe expected toxicity in overdose or therapeutic misadventure.

Functions of Selected Neurotransmitter Receptor Targets [1]

[Bolded effects are of clinical significance in the ED, but not necessarily more frequent.]

Examples of Clinical Differences Related to Receptor Profiles

1. Haloperidol and risperidone are associated with extrapyramidal symptoms (EPS) related to their high potency at the D2 dopamine receptor.
2. Olanzapine is more sedating than haloperidol because of tighter affinity at the H1 histamine receptor. It is also associated with significantly greater oxygen desaturation in the presence of alcohol intoxication likely related to this action.[2]
3. Quetiapine is a relatively weak antipsychotic at the D2 receptor, but does cause sedation related to relatively potent antihistamine activity. It is also associated with more orthostatic hypotension when taken at higher doses without titrating up.

Receptor Binding Affinities (Ki) of Selected Antipsychotics [1]

A lower number indicates tighter binding affinity (lower concentration needed to inhibit receptor). Higher doses would be necessary to obtain clinical effect at receptors with higher Ki values.

References

1. Challenges and solutions in developing new medications for schizophrenia. J Clin Psychiatry. 2010;71(10):1391-1399. PMID: 21062617
2. Wilson MP, Chen N, Vilke GM, et al. Olanzapine in ED patients: differential effects on oxygenation in patients with alcohol intoxication. Am J Emerg Med. 2012 Sep;30(7):1196-201. PMID: 22633728