ABSTRACT
Forty-three schizophrenic patients participating in this study were serotyped for human leukocyte antigens (HLA-A, -B, -C, -DR, -DQ antigens). Thirty-six of them were hospitalised in two state mental hospitals and 7 in our general hospital, psychiatric unit. The patients from our unit were typed for HLA before commencing clozapine treatment whereas the patients from state hospitals were typed after commencing treatment. Three out of 43 patients developed agranulocytosis. One had a combination of both 'high-risk' haplotypes (HLA-B16(38,39), DR4, DQ3 and HLA-DR2, DQ1), another had HLA-DR2, DQ1, whereas the last had a totally different haplotype. Between non-agranulocytic patients 1 was found to carry the HLA-B16(38,39), DR4, DQ3 haplotype and 14 (out of 40) had the HLA-DR2, DQ1. Taking into account other factors supposed to be involved (a noxious metabolite, and the presence of a humoral cytotoxic factor) we must admit that despite the finding of a high-risk haplotype in Jewish populations there are other aspects of this question awaiting clarification.
Subject(s)
Agranulocytosis/chemically induced , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , HLA Antigens/drug effects , Schizophrenia/drug therapy , Adult , Agranulocytosis/immunology , Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Female , HLA Antigens/analysis , Haplotypes , Histocompatibility Testing , Humans , Male , Middle Aged , Risk Factors , Schizophrenia/immunologyABSTRACT
Available data on the clinical effectiveness and side effects of mesoridazine are reviewed, and an attempt is made to relate clinical efficacy to phenothiazine pharmacokinetics. Both controlled and open-label clinical studies have attested to the efficacy of mesoridazine in schizophrenia, as well as certain other psychiatric disorders. Clinical observations of the effectiveness of mesoridazine in patients refractory to treatment with thioridazine and other neuroleptics may be related to its slow rate of inactivation and to the relatively large proportion of free mesoridazine that is available for penetration to the target sites in the brain.
Subject(s)
Mesoridazine/therapeutic use , Biological Availability , Brain/drug effects , Heart/drug effects , Humans , Kinetics , Mesoridazine/adverse effects , Mesoridazine/metabolism , Protein Binding , Psychotic Disorders/drug therapy , Sexual Behavior/drug effectsABSTRACT
Acute i.v. infusion but not daily oral administration of thioridazine-HCl in the dog produced EKG anomalies similar to those reported in psychiatric patients taking this drug. Lack of EKG effects after thioridazine-5-sulfoxide infusion and presence of anomalies after thioridazine at equivalent doses suggests further evaluation of the relationship between reported plasma levels of thioridazine and its ring-sulfoxide in association with EKG changes.
