Interference between anti-HLA antibodies and chlorpromazine

Abstract

IT has been suggested that the effects of chlorpromazine in man and animals are genetically influenced^1,2. In mice, genetic control of sensitivity to this drug seems to reside in two loci, the more important of which lies on chromosome 9 at about the region which controls the histo-compatibility system H2 (ref. 3). We have investigated whether the presence or absence of some alleles of the HLA system—analogous to the H2 system of mouse—correlate with individual sensitivity to the drug. We evaluated the clinical responses to chlorpromazine of 33 chronic schizophrenic subjects who had been HLA typed during previous investigations^4,5. There was a highly significant positive response to chlorpromazine in patients with the antigen HLA-A1 of the HLA-A locus (unpublished results of E.S., L. Bellodi and E. Sacchetti). A possible explanation of the correlation is that the presence of HLA-A1 on the cell membrane makes chlorpromazine bind more readily to the cell. As chlorpromazine binds to lymphocyte membranes⁶, we investigated whether or not the binding of the drug could interfere with the specific binding of anti-HLA antibodies, particularly anti-HLA-Al antisera. Furthermore, as chlorpromazine binds to the β-adrenergic cell receptors, which are also present on peripheral blood lymphocytes⁷, we also used the β-adrenergic mediators dopamine (DA) and noradrenaline (NA).