Deutsch Stephen I, Schwartz Barbara L, Schooler Nina R, Rosse Richard B, Mastropaolo John, Gaskins Brooke
Mental Health Service Line, Department of Veterans Affairs Medical Center, Washington DC 20422, USA.
Clin Neuropharmacol. 2008 Jan-Feb;31(1):34-9. doi: 10.1097/wnf.0b013e31806462ba.
Converging lines of evidence suggest pathophysiology of alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) in schizophrenia. This pilot study was designed to test the tolerability, safety, and preliminary efficacy of chronic administration of an alpha7 nAChR agonist strategy involving combination treatment of cytidine diphosphocholine (CDP-choline; 2 g/d), a dietary source of the alpha7 nAChR agonist choline, and galantamine (24 mg/d), a positive allosteric modulator of nAChRs that was prescribed to prevent choline from becoming a functional antagonist and improve the efficiency of coupling the binding of choline to channel opening. The combination of CDP-choline and galantamine was administered to 6 schizophrenic patients with residual symptoms in a 12-week, open-label trial. Patients were maintained on stable dose regimens of antipsychotic medications for 4 weeks before study entry and for the trial duration. All reached target doses of both agents and completed the trial. Transient side effects resolved without slowing of dose titration. Gastrointestinal adverse effects were most common. Of the 6 patients, 5 showed reduction in Clinical Global Impressions severity scores and Positive and Negative Syndrome Scale total scores. Three patients requested continuation of the adjunctive combination at the end of the trial. These results suggest further investigation of the combination of CDP-choline and galantamine as an alpha7 nAChR agonist intervention.
越来越多的证据表明，α7烟碱型乙酰胆碱受体（α7 nAChRs）的病理生理学与精神分裂症有关。这项初步研究旨在测试一种α7 nAChR激动剂策略长期给药的耐受性、安全性和初步疗效，该策略包括联合使用胞苷二磷酸胆碱（CDP-胆碱；2 g/天）和加兰他敏（24 mg/天），CDP-胆碱是α7 nAChR激动剂胆碱的膳食来源，加兰他敏是nAChRs的正变构调节剂，用于防止胆碱成为功能性拮抗剂并提高胆碱与通道开放结合的效率。在一项为期12周的开放标签试验中，将CDP-胆碱和加兰他敏的组合给予6名有残留症状的精神分裂症患者。在研究开始前和试验期间，患者维持稳定剂量的抗精神病药物治疗4周。所有患者均达到两种药物的目标剂量并完成试验。短暂的副作用自行缓解，剂量滴定未减慢。胃肠道不良反应最为常见。6名患者中，5名患者的临床总体印象严重程度评分和阳性与阴性症状量表总分有所降低。3名患者在试验结束时要求继续使用辅助联合治疗。这些结果表明，需要进一步研究CDP-胆碱和加兰他敏联合作为α7 nAChR激动剂干预措施。
