Effects of Short-term Administration of Antipsychotic Drugs on Lymphocyte Subsets in Schizophrenic Patients

Membrane phospholipase D (PLD) is associated with numerous neuronal functions, such as axonal growth, synaptogenesis, formation of secretory vesicles, neurodegeneration, and apoptosis. PLD acts mainly on phosphatidylcholine, from which phosphatidic acid (PA) and choline are formed. In turn, PA is a key element of the PLD-dependent secondary messenger system. Changes in PLD activity are associated with the mechanism of action of olanzapine, an atypical antipsychotic. The aim of the present study was to assess the effect of short-term administration of the first-generation antipsychotic drugs haloperidol, chlorpromazine, and fluphenazine on membrane PLD activity in the rat brain. Animals were sacrificed for a time equal to the half-life of the antipsychotic drug in the brain, then the membranes in which PLD activity was determined were isolated from the tissue. The results indicate that only haloperidol in a higher dose increases the activity of phospholipase D. Such a mechanism of action of haloperidol has not been described previously. Induction of PLD activity by haloperidol may be related to its mechanism of cytotoxicity. The finding could justify the use of PLD inhibitors as protective drugs against the cytotoxicity of first-generation antipsychotic drugs like haloperidol.

Download Full-text

Does short-term administration of glucagon-like peptide type 2 affect bone mass and markers of bone remodeling in short bowel patients?

Gastroenterology ◽

10.1016/s0016-5085(01)81558-4 ◽

2001 ◽

Vol 120 (5) ◽

pp. A314-A314

Author(s):

K HADERSLEV ◽

P JEPPESEN ◽

B HARTMANN ◽

J THULESEN ◽

J GRAFF ◽

...

Keyword(s):

Bone Mass ◽

Bone Remodeling ◽

Short Term ◽

Short Bowel ◽

Term Administration ◽

Glucagon Like Peptide

Download Full-text

Long-term Administration of Antipsychotic Drugs in Schizophrenia and Influence of Substance and Drug Abuse on the Disease Outcome

Current Drug Abuse Reviews ◽

10.2174/1874473710666171020104524 ◽

2018 ◽

Vol 10 (1) ◽

pp. 19-24

Author(s):

Felix-Martin Werner ◽

Rafael Covenas

Keyword(s):

Drug Abuse ◽

Antipsychotic Drugs ◽

Disease Outcome ◽

Term Administration

Download Full-text

Gene Frequency of CYP2D64 and 10 Variants in Karachi Population

Current Pharmacogenomics and Personalized Medicine ◽

10.2174/1875692117999201014162804 ◽

2020 ◽

Vol 17 ◽

Author(s):

Tamkeen Fatima ◽

Farah Zeb ◽

A. Dar Farooq

Keyword(s):

Antipsychotic Drugs ◽

Screening Program ◽

Restriction Enzymes ◽

Normal Subjects ◽

Control Group ◽

Poor Metabolizer ◽

Cyp2d6 Polymorphism ◽

Wild Allele ◽

Schizophrenic Patients ◽

Intermediate Metabolizer

Background: CYP2D6 is to be considered the most pronounced gene in pharmacegenetic field which is involved in metabolizing ~25% of all clinically used neuroleptic drugs and other antidepressants. We designed a study to evaluate differential expression of CYP2D6*4 and CYP2D6*10 variants which are very prevalent in Asian countries and exhibit variation in drug metabolizing ability that affect therapeutic responses. Objective: The purpose of this study is to determine the genotypic frequencies of CYP2D6 *1 (normal metabolizer), *4 (poor metabolizer) and *10 (intermediate metabolizer) variants among schizophrenic subjects and compared with control group from a sub-set of Karachi population. Method: Genomic deoxyribonucleic acid (DNA ) was extracted and amplified with CYP2D6*4 and *10 primers using polymerase chain reaction (PCR) and digested by Bacillus stereothermophilus (BstN1) and Hemophilus parahemolyticus (Hph1) restriction enzymes. The digested bands were identified as wild type or mutants and their genotypic frequencies were estimated statistically by Hardy-Weinberg equation (HWE) and analyzed further under non-parametric Chi-square test. Results: The results mentioned the frequencies of CYP2D6*1 wild allele (57%) which produces functional enzyme in normal subjects but CYP2D6*4 variant (9%) that produces non-functional enzyme and CYP2D6*10 allele (70%) produces altered enzyme with reduced activity that was most prevalent in schizophrenic patients. Conclusion : Genotyping of CYP2D6 alleles among schizophrenic patients indicated prevalence of *4 and *10 variants in Karachi population producing non-functional and reduced functional drugs metabolizing enzymes respectively that increases the incurability rate of schizophrenia. Therefore, CYP2D6 gene screening program should be conducted routinely in clinical practice to help clinicians to prescribing appropriate doses according to patient’s genotype and minimize the sufferings of schizophrenia. Discussion: In last, drug response is a complex phenomenon that is dependent on genetic and environmental factors. CYP2D6 polymorphism may un-cured the schizophrenia due to improper drug metabolism and protein-proteins interaction that may alter the antipsychotic drugs metabolism among patients with variable drug resposes. Gene testing system need to establish for analyzing maximum patient’s genotypes predicted with poor metabolizer, intermediate metabolizer and ultrarapid metabolizer for the adjustment of antipsychotic drugs.

Download Full-text