The term neuroleptic was intended to contrast the effects of drugs such as chlorpromazine to those of sedatives and other CNS depressants. The neuroleptic syndrome involves suppression of spontaneous movements and complex behaviors, whereas spinal reflexes and unconditioned nociceptive-avoidance behaviors remain intact. In humans, neuroleptic drugs reduce initiative and interest in the environment as well as manifestations of emotion. In clinical use, there may be some initial drowsiness and slowness in response to external stimuli. However, subjects are easily aroused, can answer questions, and retain intact cognition. Ataxia, incoordination, or dysarthria do not occur at ordinary doses. Typically, psychotic patients soon become less agitated, withdrawn or autistic patients sometimes become more responsive and communicative, and aggressive and impulsive behavior diminishes. Gradually (usually over days), psychotic symptoms of hallucinations, delusions, and disorganized or incoherent thinking ameliorate. Neuroleptic agents also exert characteristic neurological effects—including bradykinesia, mild rigidity, tremor, and akathisia— that resemble the signs of Parkinson's disease.
Although the term neuroleptic initially encompassed this whole unique syndrome and is still used as a synonym for antipsychotic, it now is used to emphasize the more neurological aspects of the syndrome (i.e., the parkinsonian and other extrapyramidal effects). Except for clozapine, arip-iprazole, quetiapine, ziprasidone, and low doses of olanzapine and risperidone, antipsychotic drugs available in the U.S. also have effects on movement and posture and can be called neuroleptic. The more general term antipsychotic is preferable, as reinforced by the growing number of modern atypical antipsychotic drugs with little extrapyramidal action.
BEHAVIORAL EFFECTS A number of effects in animal behavioral models have been used to predict the efficacy or potential adverse effects of antipsychotic agents. Despite their widespread use, these paradigms generally have not provided important insights into the basis for clinical antipsychotic effects.
EXTRAPYRAMIDAL EFFECTS OF ANTIPSYCHOTICS The acute adverse clinical effects of antipsychotic agents are best mimicked in animals by assessing catalepsy in rats (immobility that allows an animal to be placed in abnormal postures that persist) or dystonia in monkeys. Late dyskinetic effects of antipsychotics are represented by the development of vacuous chewing movements in rats.
A particularly disturbing adverse effect of most antipsychotics is restless activity, termed akathisia, which is not readily mimicked by animal behavior. The cataleptic immobility of animals treated with classical antipsychotics resembles the catatonia seen in some psychotic patients and in a variety of metabolic and neurological disorders affecting the CNS. In patients, catatonic signs, along with other features of psychotic illnesses, are sometimes relieved by antipsychotic agents. However, rigidity and bradykinesia, which mimic catatonia, can be induced by administering large doses of potent traditional neuroleptics and by addition of an antimuscarinic-antiparkinson agent.
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