The symptoms of Alzheimer’s disease (AD) do not include only memory loss and cognitive decline but also neuropsychiatric manifestation. These AD-related symptoms are usually treated with the aid of antipsychotics; however, their effects on cognition and safety remain unexplored. The present study determines the effects of quetiapine, an atypical antipsychotic, and two imidazo[1,2-a]pyrimidine-based inhibitors of PDE10A on the activity of human cholinesterases. Quetiapine moderately inhibited BuChE (IC₅₀ = 6.08 ± 1.64 µmol/L) but improved the anti-BuChE properties of donepezil by decreasing its IC₅₀ value. Both PDE10A inhibitors were found to possess moderate anti-AChE properties. The combined mixtures of donepezil and imidazo[1,2-a]pyrimidine analogues produce a synergistic anti-BuChE effect which was greater than either compound alone, improving the IC₅₀ value by approximately six times. These favourable interactions between quetiapine, PDE10A inhibitors and clinically approved donepezil, resulting in improved anti-BuChE activity, can lead to a wider variety of potent AD treatment options.

阿尔茨海默氏病（AD）的症状不仅包括记忆力减退和认知能力下降，还包括神经精神病学表现。这些与AD相关的症状通常可以通过抗精神病药治疗。然而，它们对认知和安全性的影响尚待探索。本研究确定了非典型抗精神病药物喹硫平和两种基于咪唑并[1,2-a]嘧啶的PDE10A抑制剂对人胆碱酯酶活性的影响。喹硫平可适度抑制BuChE（IC ₅₀ = 6.08±1.64 µmol / L），但可通过降低多奈哌齐的IC _50来提高其抗BuChE性能。值。发现两种PDE10A抑制剂均具有中等的抗AChE特性。多奈哌齐和咪唑并[1,2-a]嘧啶类似物的混合混合物产生协同抗-BuChE效应，比单独使用任何一种化合物都大，将IC ₅₀值提高了约六倍。喹硫平，PDE10A抑制剂与临床批准的多奈哌齐之间的这些有利相互作用，导致改善的抗BuChE活性，可导致更广泛的有效AD治疗选择。