Chapter 3. Antipsychotic Agents

Abstract

Publisher Summary Noninvasive radioimaging techniques have brought new insight into the role of the regional distribution and receptor binding of anti-psychotic agents. Studies of the blood flow in the brains of schizophrenic patients with positron-emitting xenon-133 have revealed an over-activation in the left hemisphere during performance of a spatial line orientation test. Positron emission tomography (PET) scanning with oxygen-15 (half-life 123s) in some schizophrenic patients failed to support the hypothesis of reduced blood flow in frontal cortex. Haloperidol-induced dopamine (DA) receptor supersensitivity in schizophrenics appears to be attenuated by concurrent treatment with lithium. The DA hypothesis of schizophrenia has been reviewed in the light of recent findings. Perioral dyskinesias can be induced acutely in rats by the DA antagonists' spiroperidol and sulpiride, and by the selective agonist SKF 38393 but not by the selective agonist LY 141865. Attempts to separate the multitude of effects shown by cyproheptadine have included the introduction of nuclear substituents and replacement of a benzene ring by a pyrrole ring. The conformational flexibility was higher for these new pyrrolo-compounds than for the corresponding cyproheptadine derivatives as evidenced from the rates of racemization of the atropisomers. This chapter discusses the accumulated experience with depot neuroleptics, such as clopenthixol decanoate and pipotiazine palmitate. The anti-hallucinator effect of chlorpromazine correlates with the serum levels of prolactin consistent with the DA hypothesis of schizophrenia. No regional site specificity for limbic areas was found with thioridazine or with clozapine. The chapter discusses the anti-psychotic agents through phenothiazines and related rigid compounds, diphenvlpiperidines and butyrophenones, substituted benzamides, and miscellanious compounds.