Positive allosteric modulators (PAMs) of alpha 7 nicotinic acetylcholine receptors (α7-nAChRs) may represent a novel approach to attenuate cognitive decline in Alzheimer's disease (AD). One possible scenario for the use of this class of compounds is their combination with currently approved anti-AD drugs. We thus evaluated the efficacy of co-administration of inactive doses of type I and type II α7-nAChR PAMs (CCMI and PNU-120596, respectively) with acetylcholinesterase inhibitors (AChEIs), donepezil and galantamine, or with a non-competitive glutamate N-methyl-D-aspartate receptor antagonist, memantine, in ameliorating scopolamine-induced memory deficits in the novel object recognition test in rats. Both CCMI and PNU-120596 as well as donepezil, galantamine and memantine attenuated the scopolamine-induced recognition impairments. Interestingly, the combined administration of previously established sub-effective doses of the tested PAMs (0.1 mg/kg) with either AChEIs, donepezil (0.3 mg/kg) and galantamine (0.1 mg/kg), or memantine (0.3 mg/kg) also restored object recognition memory in scopolamine-treated animals. These findings suggest the therapeutic potential of α7-nAChR PAMs as an augmentation strategy for cognitive enhancement in AD.

中文翻译：

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α7烟碱乙酰胆碱受体的正构构调节剂可增强东anti碱治疗的大鼠中常规抗阿尔茨海默病药物的认知作用。

α7烟碱乙酰胆碱受体（α7-nAChRs）的正变构调节剂（PAM）可能代表一种减轻阿尔茨海默氏病（AD）认知能力下降的新方法。使用此类化合物的一种可能情况是将其与目前批准的抗AD药物联合使用。因此，我们评估了非活性剂量的I型和II型α7-nAChRPAM（分别为CCMI和PNU-120596）与乙酰胆碱酯酶抑制剂（AChEI），多奈哌齐和加兰他敏或与非竞争性谷氨酸N并用的疗效-甲基-D-天门冬氨酸受体拮抗剂美金刚在减轻大鼠新能源物体识别试验中东amine碱引起的记忆障碍中的作用。CCMI和PNU-120596以及多奈哌齐，加兰他敏和美金刚都减弱了东pol碱引起的识别障碍。有趣的是，先前建立的亚有效剂量的受测PAM（0.1 mg / kg）与AChEI，多奈哌齐（0.3 mg / kg）和加兰他敏（0.1 mg / kg）或美金刚（0.3 mg / kg）联合给药还可以恢复东treated碱治疗动物的物体识别记忆。这些发现暗示了α7-nAChRPAM作为AD认知增强的增强策略的治疗潜力。