Chapter 5. Novel Antipsychotics

Abstract

This chapter describes the novel atypical anti-psychotic agents that are used in treating schizophrenia. Use of such agents is also popular because of their reduced side effects compared to other similar agents. Newly identified dopamine receptors (D3, D4, D5), which were further characterized, has included the first autoradiographic visualization of D3 receptors in rat and human brain. The D4 receptor has been found to exist as several polymorphic variants that may explain the genetic range of susceptibility to schizophrenia and/or varied individual response to anti-psychotics. Researchers have measured the levels of messenger RNA (mRNA) for D1, D2, D3, and D5 receptors in the rat brain after neuroleptic treatment. Clinical trials with roxindole, a D2 autoreceptor agonist, showed efficacy in a group of schizophrenic patients with primary negative symptoms, whereas, results with SDZ-HDZ912 have been less conclusive. The virtues of this atypical anti-psychotic continue to be extolled. Debate on the novel mechanisrn(s) of action of clozapine continues: its superior efficacy has been attributed to interactions with a variety of receptor sites in the CNS and this list has been expanded to include 5HT 1c , D 4 , and glutamate. The chapter also discusses the role of serotonine antagonists, sigma receptors, neurokinin, and others. Several additional receptors have been proposed as having a potential role in the alleviation of psychotic symptoms. The genetic factor in the development of schizophrenia has been further emphasized as has the incidence of the disease because of prior exposure to viral pathogens. Other biological findings like the interaction of neuroleptics with the CNS receptors utilizing positron emission tomography (PET) and magnetic resonance imaging (MRI) techniques, and molecular modeling studies have also got their significance.