PubMed · 1679676
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D F Dunne. 1991. Prescribing practices.. https://doi.org/10.1192/bjp.159.1.156a
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The atypical neuroleptic clozapine is thought to exert its psychopharmacological actions through a variety of neurotransmitter receptors. It binds preferentially to D4 and 5-HT2 receptors; however, little is known on it's interaction with the 5-HT3 receptor. Using a cell line stably expressing the 5-HT3 receptor, whole-cell voltage-clamp analysis revealed functional antagonistic properties of clozapine at low nanomolar concentrations in view of a binding affinity in the upper nanomolar range. Because the concentration of clozapine required for an interaction with the 5-HT3 receptor can be achieved with therapeutical doses, functional antagonistic properties at this ligand-gated ion channel may contribute to its unique psychopharmacological profile.
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Clozapine is an atypical antipsychotic with a low extrapyramidal side effect profile, and is often useful in the treatment of schizophrenics who do not respond to classical neuroleptics. While the dopamine D2-receptor is believed to be the primary target of classical neuroleptics, clozapine has greater affinity to the dopamine D4-receptor (DRD4). Great variability has been reported for the DRD4 gene and in the receptor itself. It is now possible to investigate if this variation influences individual differences in response to clozapine treatment or in the genetic susceptibility to schizophrenia. Till now the examined variations in the DRD4 gene do not seem to influence response to clozapine treatment or genetic susceptibility to schizophrenia. However, some of clozapine's side effects might be mediated through DRD4 binding.