title: Antipsychotic drugs influence transport of the beta-adrenergic antagonist [3H]-dihydroalprenolol into neuronal and blood cells.
abstract: The amine hypothesis suggests that the cause of schizophrenic or depressive psychosis is dysfunction of noradrenergic or serotonergic neurotransmission. We investigated pharmacological properties of [3H]-dihydroalprenolol (DHA) transport into C6, IMR32, native lymphocytes, B-lymphoblastoids and MOLT-3 cells. DHA transport was inhibited by a heterogeneous group of structurally related compounds exhibiting an amine group and various aromatic ring structures. It was verified on cells of neuronal/glial and blood cell origin but in detail on B-lymphoblastoids. The latter once showed strongest inhibition of DHA transport using tricyclic antidepressants (amitriptyline: IC50 = 2.86 microM, imipramine: IC50 = 3.33 microM) and haloperidol (IC50 = 3.98 microM) as a neuroleptic. Antipsychotics like clozapine (IC50 = 11 microM), olanzapine (IC50 = 15 microM), spiperone (IC50 = 66 microM) and EMD 49980 (ICso >> 100 microM) were less effective. In contrast to cells of blood origin, a stimulation of DHA transport by antipsychotics was not detectable using neuronal cells. As antipsychotics showed a distinct inhibition and, concerning cells of blood origin, a stimulation of transport after pre-incubation, further investigations seem to be of interest in respect to its involvement in the cellular uptake of drugs and therefore its impact on the quality of therapy of psychiatric patients.
authors.affiliation: Neurobiochemical Research Unit, Department of Psychiatry, Heinrich-Heine-University Düsseldorf, Bergische Landstrasse 2, 40629 Duesseldorf, Germany. Klaus.Krieger@lvr.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Krieger
authors.forename: Ansgar
authors.initials: A
authors.lastname: Klimke
authors.forename: Uwe
authors.initials: U
authors.lastname: Henning
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D004082:Dihydroalprenolol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects*; D006801:Humans; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D011618:Psychotic Disorders / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology*; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D012701:Serotonin; D004082:Dihydroalprenolol; D009638:Norepinephrine