赛洛西宾 | 520-52-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 赛洛西宾
• 中文别名: 叔胺吲哚磷酯；西洛西宾；塞洛西宾
• 英文名称: psilocybin
• 英文别名: [3-(2-dimethylaminoethyl)-1H-indol-4-yl] dihydrogen phosphate；4-phosphoryloxy-N,N-dimethyltryptamine；Psilocybine；[3-[2-(dimethylazaniumyl)ethyl]-1H-indol-4-yl] hydrogen phosphate
• CAS: 520-52-5
• 化学式: C₁₂H₁₇N₂O₄P
• 分子量: 284.252
• InChiKey: QVDSEJDULKLHCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  85.8
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

代谢

赛洛西宾在体内迅速且完全地水解成赛洛辛。

Psilocybin is rapidly and completely hydrolyzed to psilocin in vivo.

来源:Hazardous Substances Data Bank (HSDB)

代谢

赛洛西宾（Psilocybin）在体内迅速脱磷酸化成为赛洛辛（psilocin）。赛洛西宾主要在肝脏代谢，转化为赛洛辛。它会被单胺氧化酶分解。（L1143）

Psilocybin is rapidly dephosphorylated in the body to psilocin. Psilocybin is metabolized mostly in the liver where it becomes psilocin. It is broken down by the enzyme monoamine oxidase. (L1143)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

赛洛西宾（Psilocybin）在体内迅速脱磷酸化成为赛洛辛（psilocin），后者在大脑中作为5-HT2A血清素受体的部分激动剂，模仿血清素（5-HT）的效果。赛洛辛是5-HT1A和5-HT2A/2C的激动剂。

Psilocybin is rapidly dephosphorylated in the body to psilocin which then acts as a partial agonist at the 5-HT2A serotonin receptor in the brain where it mimics the effects of serotonin (5-HT). Psilocin is an 5-HT1A and 5-HT2A/2C agonist. (L1143)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

裸头菌碱具有神经毒性并产生幻觉。

Psilocybin is neurotoxic and produces hallucinations. (L1143)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服、皮肤、吸入和 parenteral（被污染的药物）。 (A3101)

Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

最初，受试者可能会开始感到有些迷茫、昏昏欲睡、情绪愉快或有时抑郁。在低剂量下，可能会出现幻觉效果，包括颜色增强和几何形状的动画效果。闭眼幻觉可能会发生，受影响的个体可能会看到多色几何形状和生动的想象序列。在较高剂量下，幻觉效果增强，体验趋向于更内省或精神活性，较少社交。睁眼视觉更常见，可能非常详细，尽管很少与现实混淆。

Initially the subject may begin to feel somewhat disoriented, lethargic, and euphoric or sometimes depressed. At low doses, hallucinatory effects may occur, including enhancement of colors and the animation of geometric shapes. Closed-eye hallucination may occur, where the affected individual may see multi-coloured geometric shapes and vivid imaginative sequences. At higher doses, hallucinatory effects increase and experiences tend to be less social and more introspective or entheogenic. Open-eye visuals are more common, and may be very detailed although rarely confused with reality. (L1143)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

在一项临床研究中，八名志愿者接受了口服活性剂量为212±25微克/千克体重的赛洛西宾。为了研究赛洛辛，即赛洛西宾的第一个代谢物，的消除动力学，收集了24小时的尿液，并通过带有柱切换和电化学检测的高效液相色谱（HPLC-ECD）测定了赛洛辛的浓度。样品处理包括使用抗坏血酸保护不稳定的赛洛辛，冻干，以及用甲醇提取。在2-4小时收集间隔的尿样中，赛洛辛的峰值浓度达到了870微克/升。在这个时期，赛洛辛的排泄率为55.5±33.8微克/小时。定量限（10微克/升）通常在药物给药后24小时达到。在24小时内，应用的赛洛西宾剂量的3.4±0.9%以自由赛洛辛的形式被排泄。向尿样中加入β-葡萄糖醛酸酶并在40°C下孵化5小时，导致赛洛辛浓度增加两倍，尽管在孵化过程中有18±7%的未结合PI分解。/总之/，在人类中，赛洛辛部分以赛洛辛-O-葡萄糖醛酸苷的形式被排泄，并且酶促水解延长了尿样中赛洛辛的可检测时间。

In a clinical study eight volunteers received psilocybin in psychoactive oral doses of 212+ or -25 ug/kg body weight. To investigate the elimination kinetics of psilocin, the first metabolite of psilocybin, urine was collected for 24 hr and psilocin concentrations were determined by high-performance liquid chromatography with column switching and electrochemical detection (HPLC-ECD). Sample workup included protection of the unstable psilocin with ascorbic acid, freeze-drying, and extraction with methanol. Peak psilocin concentrations up to 870 ug/l were measured in urine samples from the 2-4 hr collection interval. The psilocin excretion rate in this period was 55.5+ or -33.8 microg/h. The limit of quantitation (10 ug/L) was usually reached 24 hr after drug administration. Within 24 hr, 3.4+ or -0.9% of the applied dose of psilocybin was excreted as free psilocin. Addition of beta-glucuronidase to urine samples and incubation for 5 hr at 40 degrees C led to twofold higher psilocin concentrations, although 18+ or -7% of the amount of unconjugated PI was decomposed during incubation. /In conclusion/ that in humans psilocin is partially excreted as psilocin-O-glucuronide and that enzymatic hydrolysis extends the time of detectability for psilocin in urine samples.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  赛洛西宾 在 alkaline phosphatase 作用下， 生成 4-羟基-N,N-二甲基色胺
  参考文献：
  名称：

  10.1111/bph.16466

  摘要：

  Background and PurposeDemand for new antidepressants has resulted in a re‐evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin‐containing “magic” mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacological and behavioural effects.Experimental ApproachWe compared baeocystin, norbaeocystin and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, similarly penetrate the blood–brain barrier, serve as ligands for similar receptors and modulate behaviour in rodents similarly. We also assessed the stability and optimal storage and handling conditions for each compound.Key ResultsIn vitro enzyme kinetics assays found that all compounds had nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin crossed a blood–brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. The dephosphorylated form of norbaeocystin was found to activate the 5‐HT2A receptor with similar efficacy to psilocin and norpsilocin in in vitro cell imaging assays. Behaviourally, only psilocybin induced head twitch responses in rats, a marker of 5‐HT2A‐mediated psychedelic effects and hallucinogenic potential. However, like psilocybin, norbaeocystin improved outcomes in the forced swim test. All compounds caused minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles.Conclusions and ImplicationsCollectively, this work suggests that other naturally occurring tryptamines, especially norbaeocystin, may share overlapping therapeutic potential with psilocybin, but without causing hallucinations.

  DOI：

  10.1111/bph.16466
• 作为产物：
  描述：

  3-(2-氨基乙基)-1H-吲哚-7-醇 在 5’-三磷酸腺苷 作用下， 以 aq. buffer 为溶剂， 反应 8.0h， 生成 赛洛西宾
  参考文献：
  名称：

  色氨酸合酶增强反应中裸盖菇素及其衍生物的生物催化生产

  摘要：

  裸盖菇素（4-磷酸氧基-N，N-二甲基色胺）是裸盖菇属真菌的主要生物碱，即所谓的“神奇蘑菇”。这种精神药物天然产品作为未来治疗抑郁症和焦虑症的药物的药学兴趣正在重新出现。在这里，我们通过将 TrpB（蘑菇Psilocybe cubensis的色氨酸合酶）添加到反应中，提出了一种增强的裸盖菇素生产酶促途径。我们利用其底物灵活性并展示了 4-羟基吲哚和l的裸盖菇素形成-丝氨酸，与以前的方法相比，它们是成本较低的底物。此外，我们通过相同的体外方法展示了 7-磷酸氧色胺（异降贝藻素）的酶促生产，这是裸盖菇生物碱降贝藻素（4-磷酸氧色胺）的一种非天然同类物，以及血清素（5-羟色胺）。

  DOI：

  10.1002/chem.201801047

文献信息

• [EN] CANNABINOID DERIVATIVES<br/>[FR] DÉRIVÉS CANNABINOÏDES
  申请人：CANOPY GROWTH CORP

  公开号：WO2021113958A1

  公开（公告）日：2021-06-17

  This disclosure relates generally to cannabinoid derivatives, pharmaceutical compositions comprising them, and methods of using the cannabinoid derivatives.

  这份公开文件通常涉及大麻素衍生物、包含它们的药物组合物以及使用大麻素衍生物的方法。
• [EN] 5-HT2C RECEPTOR AGONISTS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] AGONISTES DE RÉCEPTEUR 5-HT2C ET COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：ARENA PHARM INC

  公开号：WO2017023679A1

  公开（公告）日：2017-02-09

  Provided in some embodiments are compounds of Formula A, as defined herein, that modulate the activity of 5-HT2C receptor. Also provided in some embodiments are methods, such as, for weight management, inducing satiety, and decreasing food intake, and for preventing and treating obesity, antipsychotic-induced weight gain, type 2 diabetes, Prader-Willi syndrome, tobacco/nicotine dependence, drug addiction, alcohol addiction, pathological gambling, reward deficiency syndrome, and sex addiction), obsessive-compulsive spectrum disorders and impulse control disorders (including nail-biting and onychophagia), sleep disorders (including insomnia, fragmented sleep architecture, and disturbances of slow-wave sleep), urinary incontinence, psychiatric disorders (including schizophrenia, anorexia nervosa, and bulimia nervosa), Alzheimer disease, sexual dysfunction, erectile dysfunction, epilepsy, movement disorders (including parkinsonism and antipsychotic-induced movement disorder), hypertension, dyslipidemia, nonalcoholic fatty liver disease, obesity-related renal disease, and sleep apnea.

  在某些实施例中提供了一些符合本文所定义的A式化合物，其调节5-HT2C受体的活性。在某些实施例中还提供了一些方法，例如用于体重管理、诱导饱腹感、减少食物摄入，以及预防和治疗肥胖、抗精神病药物引起的体重增加、2型糖尿病、普拉德-威利综合征、烟草/尼古丁依赖、药物成瘾、酒精成瘾、病理性赌博、奖赏缺乏综合征和性成瘾，强迫症谱系障碍和冲动控制障碍（包括咬指甲和咬甲症），睡眠障碍（包括失眠、睡眠结构碎裂和慢波睡眠紊乱），尿失禁，精神障碍（包括精神分裂症、厌食症和暴食症），阿尔茨海默病，性功能障碍，勃起功能障碍，癫痫，运动障碍（包括帕金森病和抗精神病药物引起的运动障碍），高血压，血脂异常，非酒精性脂肪肝病，肥胖相关肾脏疾病和睡眠呼吸暂停症。
• [EN] CANNABIGEROL DERIVATIVES AND USE THEREOF AS CANNABINOID RECEPTOR MODULATORS<br/>[FR] DÉRIVÉS DE CANNABIGÉROL ET LEUR UTILISATION EN TANT QUE MODULATEURS DES RÉCEPTEURS CANNABINOÏDES
  申请人：CANOPY GROWTH CORP

  公开号：WO2021102567A1

  公开（公告）日：2021-06-03

  The synthesis of a range of pentylbezene- 1,3-diol compounds of formula I is disclosed. These compounds bind to cannabinoid 1 and 2 receptors (CB1 and CB2), and are thus presumed to be useful in modulating the activity of such receptors. Accordingly, the use of such synthetic cannabinoids in the treatment of various disorders mediated by CB1 and CB2 is contemplated.

  揭示了一系列式I的戊基苯-1,3-二醇化合物的合成。这些化合物与大麻素1和2受体（CB1和CB2）结合，因此被认为在调节这些受体的活性方面是有用的。因此，考虑了在治疗由CB1和CB2介导的各种疾病中使用这种合成大麻素。
• [EN] COMPOSITIONS AND METHODS THEREOF<br/>[FR] COMPOSITIONS ET PROCÉDÉS ASSOCIÉS
  申请人：EXCIVA UG HAFTUNGSBESCHRAENKT

  公开号：WO2018039642A1

  公开（公告）日：2018-03-01

  Compounds of formula I, (I) or enantiomers thereof, metabolites thereof, derivatives thereof, deuterated derivatives thereof, halogenated derivatives thereof, prodrugs thereof, pharmaceutically acceptable salts thereof, N- oxides thereof, or a combination thereof, processes and intermediates for preparation thereof, compositions thereof, and uses thereof, are provided. Pharmaceutical compositions comprising a compound of formula I and a compound of Formula II: (IIa) (IIb) or enantiomers thereof, metabolites thereof, derivatives thereof, deuterated derivatives thereof, prodrugs thereof, pharmaceutically acceptable salts thereof, N-oxides thereof, or a combination thereof. Compositions and methods for improving the efficacy of DEX, or providing beneficial pharmacokinetic effects to DEX, comprising co-administering a compound of formula I or SARPO, and a compound of Formula II or DEX to a subject in need thereof, and dosage forms, drug delivery systems, methods of treatment thereof.

  提供具有公式I的化合物(I)或其对应异构体、代谢物、衍生物、氘化衍生物、卤化衍生物、前药、药用可接受盐、N-氧化物或其组合，以及它们的制备过程和中间体、组合物和使用方法。包含公式I化合物的药物组合物以及公式II的化合物(IIa) (IIb)或其对应异构体、代谢物、衍生物、氘化衍生物、前药、药用可接受盐、N-氧化物或其组合。包含共给予需要该物质的受试者公式I化合物或SARPO和公式II化合物或DEX的DEX效能改进或提供DEX有益药代动力学效果的组合物和方法，以及剂量形式、药物传递系统、治疗方法。
• Methods for Treating Dependence
  申请人：Woiwode Tom

  公开号：US20090041800A1

  公开（公告）日：2009-02-12

  Provided are methods of treating patients suffering from or susceptible to at least one symptom of abuse of, dependence on, or withdrawal from at least one substance with Compound A. Also provided are methods of treating at least one phase of substance dependence on at least one substance in patients and certain methods of treating at least one phase of cocaine dependence in patients.

  提供了使用化合物A治疗患有或易受至少一种物质滥用、依赖或戒断症状的患者的方法。还提供了治疗患者至少一种物质依赖的方法以及治疗患者可卡因依赖至少一种阶段的方法。

表征谱图