Barrett S L, Bell R, Watson D, King D J
Department of Therapeutics and Pharmacology, Queens University Belfast, Belfast, UK.
J Psychopharmacol. 2004 Jun;18(2):156-72. doi: 10.1177/0269881104042614.
In view of the evidence that cognitive deficits in schizophrenia are critically important for long-term outcome, it is essential to establish the effects that the various antipsychotic compounds have on cognition, particularly second-generation drugs. This parallel group, placebo-controlled study aimed to compare the effects in healthy volunteers (n = 128) of acute doses of the atypical antipsychotics amisulpride (300 mg) and risperidone (3 mg) to those of chlorpromazine (100 mg) on tests thought relevant to the schizophrenic process: auditory and visual latent inhibition, prepulse inhibition of the acoustic startle response, executive function and eye movements. The drugs tested were not found to affect auditory latent inhibition, prepulse inhibition or executive functioning as measured by the Cambridge Neuropsychological Test Battery and the FAS test of verbal fluency. However, risperidone disrupted and amisulpride showed a trend to disrupt visual latent inhibition. Although amisulpride did not affect eye movements, both risperidone and chlorpromazine decreased peak saccadic velocity and increased antisaccade error rates, which, in the risperidone group, correlated with drug-induced akathisia. It was concluded that single doses of these drugs appear to have little effect on cognition, but may affect eye movement parameters in accordance with the amount of sedation and akathisia they produce. The effect risperidone had on latent inhibition is likely to relate to its serotonergic properties. Furthermore, as the trend for disrupted visual latent inhibition following amisulpride was similar in nature to that which would be expected with amphetamine, it was concluded that its behaviour in this model is consistent with its preferential presynaptic dopamine antagonistic activity in low dose and its efficacy in the negative symptoms of schizophrenia.
鉴于有证据表明精神分裂症中的认知缺陷对长期预后至关重要，因此确定各种抗精神病药物，尤其是第二代药物对认知的影响非常必要。这项平行组、安慰剂对照研究旨在比较急性剂量的非典型抗精神病药物氨磺必利（300毫克）、利培酮（3毫克）和氯丙嗪（100毫克）对128名健康志愿者在与精神分裂症过程相关测试中的影响：听觉和视觉潜在抑制、听觉惊吓反应的前脉冲抑制、执行功能和眼球运动。通过剑桥神经心理测试电池和言语流畅性FAS测试测量发现，所测试的药物未影响听觉潜在抑制、前脉冲抑制或执行功能。然而，利培酮破坏了视觉潜在抑制，氨磺必利显示出破坏视觉潜在抑制的趋势。虽然氨磺必利不影响眼球运动，但利培酮和氯丙嗪均降低了扫视峰值速度并增加了反扫视错误率，在利培酮组中，这与药物引起的静坐不能相关。得出的结论是，这些药物的单次剂量似乎对认知影响不大，但可能根据它们产生的镇静和静坐不能程度影响眼球运动参数。利培酮对潜在抑制的影响可能与其血清素能特性有关。此外，由于氨磺必利后视觉潜在抑制破坏的趋势在性质上与苯丙胺预期的相似，因此得出结论，其在该模型中的行为与其在低剂量时优先的突触前多巴胺拮抗活性及其在精神分裂症阴性症状中的疗效一致。
