A Review of Current Drug Targets and Pharmacology of Antipsychotic Treatment

Abstract

With the use of chlorpromazine and other traditional antipsychotics for psychosis, it was soon discovered that the antipsychotic efficacy of this class of medications was closely associated with their ability to block dopamine D 2 receptors in the brain. This prompted the hypothesis that the etiology of schizophrenia and other psychotic illnesses might be caused by a dysregulation of dopamine. This hypothesis, that the dopamine system explains schizophrenia symptoms, however, is far from complete and the treatment with conventional antipsychotic medications is far from ideal. There has been a great deal of speculation regarding the role of serotonin receptor antagonism in regards to antipsychotic effects. The second-generation antipsychotics (SGAs), clozapine, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole generally have relatively high serotonin to dopamine binding ratios. Serotonin receptor binding may be important to these drugs' actions, possibly by stimulating dopamine activity in mesocortical pathways. Yet, while the mechanism of action of SGAs as a group remain unsolved, it is important to note that the SGAs offer many clinical benefits to treatment as compared to traditional antipsychotics and are quickly emerging as first-line therapy for schizophrenia. In addition to lower rates of EPS and tardive dyskinesia, other benefits to treatment with this class of antipsychotics include better treatment of negative symptoms, better compliance, possible benefits for cognitive impairments, lower rates of relapse and rehospitalization, and more cost-effective therapy. Within the class of SGAs, however, differences exist both in efficacy and side effects and these will be described. Optimization of treatment and understanding the exact mechanism of action of current antipsychotic medications will help pave the way for new drug targets in the future.

Antipsychotic and Antiepileptic Drugs in Bipolar Disorder: The Importance of Therapeutic Drug Monitoring

“…Fig. (1b)) is one of the atypical antipsychotic drugs, also termed secondgeneration antipsychotics (SGAs) [72]. It has been marketed by Lilly & Co. in 1996 for the treatment of schizophrenia; more recently, the FDA approved OLA for the treatment of bipolar disorder [73], precisely in March 2000 for the shortterm treatment of acute manic episodes associated with bipolar disorder, in July 2003 for the use in combination with lithium or valproate for the treatment of acute manic episodes associated with bipolar disorder and in January 2004 for maintenance treatment of bipolar disorder [74].…”