Scopolamine (Hyoscine)

Scopolamine (Hyoscine) is a natural tropane alkaloid and a high-affinity competitive muscarinic acetylcholine receptor (mAChRs) antagonist^[1]. Scopolamine reversibly inhibits 5-HT3 receptor responses with an IC₅₀ value of 2.09μM^[2]. Scopolamine reduces the effects of the neurotransmitter acetylcholine (ACh) by blocking central and peripheral cholinergic signaling and is clinically used to prevent and treat motion sickness and postoperative nausea and vomiting (PONV)^[3]. Scopolamine can be used to induce cognitive impairment in experimental models because it easily penetrates the blood-brain barrier^[4].

In vivo, Scopolamine (1mg/kg) treated by intraperitoneal injection in adult male ICR mice for 4 weeks significantly interfered with the proliferation, differentiation and migration of neurons in the dentate gyrus of the mouse hippocampus, but did not induce cell death^[5]. Scopolamine (25μg/kg) treated by intraperitoneal injection in adult SD rats rapidly increased mammalian target of rapamycin complex 1 (mTORC1) signaling in prefrontal cortex (PFC) neurons and increased the number of spinal synapses in PFC neurons^[6].

References:
[1] Bubser M, Byun N, Wood M R, et al. Muscarinic receptor pharmacology and circuitry for the modulation of cognition[J]. Muscarinic receptors, 2012: 121-166.
[2] WINK M. Universität Heidelberg, Institut für Pharmazeutische Biologie, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany[J]. Bioactive Natural Products (Part B): V21, 2000, 21: 3.
[3] Coluzzi F, Rocco A, Mandatori I, et al. Non-analgesic effects of opioids: opioid-induced nausea and vomiting: mechanisms and strategies for their limitation[J]. Current Pharmaceutical Design, 2012, 18(37): 6043-6052.
[4] Chen W N, Yeong K Y. Scopolamine, a toxin-induced experimental model, used for research in Alzheimer’s disease[J]. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 2020, 19(2): 85-93.
[5] Yan B C, Park J H, Chen B H, et al. Long-term administration of scopolamine interferes with nerve cell proliferation, differentiation and migration in adult mouse hippocampal dentate gyrus, but it does not induce cell death[J]. Neural Regeneration Research, 2014, 9(19): 1731-1739.
[6] Voleti B, Navarria A, Liu R J, et al. Scopolamine rapidly increases mammalian target of rapamycin complex 1 signaling, synaptogenesis, and antidepressant behavioral responses[J]. Biological psychiatry, 2013, 74(10): 742-749.

Scopolamine (Hyoscine)是一种天然托烷类生物碱，是一种高亲和力的竞争性毒蕈碱型乙酰胆碱受体（mAChRs）拮抗剂^[1]。Scopolamine以可逆方式抑制5-HT₃受体反应，其IC₅₀值为2.09μM^[2]。Scopolamine通过阻断中枢和外周胆碱能信号传递，减少神经递质乙酰胆碱（ACh）的效应，临床上可用于预防和治疗晕动症、术后恶心呕吐（PONV）^[3]。Scopolamine能够被用来在实验模型中诱发认知障碍，因为它很容易渗透到血脑屏障中^[4]。

在体内，Scopolamine（1mg/kg）通过腹腔注射处理成年雄性ICR小鼠4周，显著干扰了小鼠海马齿状回中神经细胞的增殖、分化和迁移，但不会诱导细胞死亡^[5]。Scopolamine（25μg/kg）通过腹腔注射处理成年SD大鼠，迅速增加了前额叶皮层（PFC）神经元中哺乳动物雷帕霉素靶蛋白复合物1（mTORC1）信号传导，增加了PFC神经元中脊柱突触的数量^[6]。