Functional antagonistic properties of clozapine at the 5-HT3 receptor.
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.
Hermann
B
B
Clinical Institute, Max Planck Institute of Psychiatry, Munich, Germany.
Wetzel
C H
CH
Pestel
E
E
Zieglgänsberger
W
W
Holsboer
F
F
Rupprecht
R
R
D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D002460:Cell Line; D003024:Clozapine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D007473:Ion Channels; D008024:Ligands; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; C059068:GR 65630; D003024:Clozapine