Antipsychotic drugs influence transport of the β-adrenergic antagonist [3H]-dihydroalprenolol into neuronal and blood cells

Summary 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 μM, imipramine: IC50=3.33 μM) and haloperidol (IC50=3.98 μM) as a neuroleptic. Antipsychotics like clozapine (IC50=11 μM), olanzapine (IC50=15 μM), spiperone (IC50=66 μM) and EMD 49980 (IC50 > 100 μM) 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.