N,N-二甲基色胺 | 61-50-7

• 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: N,N-二甲基色胺
• 中文别名: N,N-二甲基-1H-吲哚-3-乙胺；二甲色胺
• 英文名称: N,N-dimethyltryptamine
• 英文别名: DMT；dimethyltryptamine；2-(1H-indol-3-yl)-N,N-dimethylethanamine；2-(1H-indol-3-yl)-N,N-dimethylethan-1-amine
• CAS: 61-50-7
• 化学式: C₁₂H₁₆N₂
• 分子量: 188.272
• InChiKey: DMULVCHRPCFFGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

经腹腔给药后，5-甲氧基-N,N-二甲基色胺和N,N-二甲基色胺在所检测的所有组织中均呈现出非常迅速的吸收和清除。当前的体内研究证实了之前的体外观察，即这些化合物的代谢途径包括氧化脱氨、N-去甲基化、O-去甲基化和N-氧化。通过对各种组织中的代谢轮廓进行分析，识别出了N-氧化物作为主要代谢物...

Following intraperitoneal administration, 5-methoxy-N,N-dimethyltryptamine and N,N-dimethyltryptamine are subject to both a very rapid uptake into, and clearance from, all tissues examined. The current studies in vivo confirm previous in vitro observations that the routes involved in the metabolism of these compounds include oxidative deamination, N-demethylation, O-demethylation, and N-oxidation. The analysis of metabolic profiles in various tissues led to the identification of the N-oxides as major metabolites...

来源:Hazardous Substances Data Bank (HSDB)

代谢

... /来自/ ... 从三名服用过死藤水的个体收集的尿样 ... /作者/ 显示，死藤水中致幻成分的主要代谢物，N,N-二甲基色胺（DMT），是其相应的N-氧化物... 此外，尽管死藤水中含有哈玛拉生物碱，能够抑制单胺氧化酶，但在尿液中检测到的DMT非常少。...

... /From/ ... urine samples collected from three individuals that were administered ayahuasca ... /authors/ show that the major metabolite of the hallucinogenic component of ayahuasca, N,N-dimethyltryptamine (DMT), is the corresponding N-oxide... Further, very little DMT was detected in urine, despite the inhibition of monoamine oxidase afforded by the presence of the harmala alkaloids in ayahuasca. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

N,N-二甲基色胺（DMT）的行为方面和代谢命运在用beta-二乙氨基乙基-二苯基丙酸酯（SKF 525-A）、异烟肼或氯丙嗪（CPZ）预处理的小鼠中进行了研究。...以10和25毫克/千克DMT的剂量，测量了DMT在大脑、血浆和肝脏水平上的剂量依赖性增加以及快速摄取和消失。...研究结果表明，DMT主要被单胺氧化酶代谢，而不是被药物代谢的肝微粒体酶代谢，并且DMT引起的行为效应是由母体化合物而不是其代谢物引起的。

Behavioral aspects and metabolic fate of N,N-dimethyltryptamine (DMT) were studied in mice pretreated with beta-diethylaminoethyl-diphenylpropylacetate (SKF 525-A), iproniazid or chlorpromazine (CPZ.). ... Dose-dependent increases with rapid uptake and disappearance in the brain, plasma and hepatic levels of DMT were measured with doses of 10 and 25 mg/kg DMT. ... It is concluded that DMT is metabolized chiefly by monoamine oxidase rather than by drug-metabolizing hepatic microsomal enzymes and that DMT-induced behavioral effects are due to the parent compound rather than its metabolite.

来源:Hazardous Substances Data Bank (HSDB)

代谢

使用氚标记的DMT和DMT-N-氧化物（DMT-NO）进行了研究，并使用薄层色谱和液体闪烁计数技术对代谢物进行了鉴定和定量。通过将四氘代DMT（DDMT）与全脑匀浆一起孵化，然后进行气相色谱/质谱分析，获得了代谢物的确认。DMT的代谢物被鉴定为吲哚乙酸（IAA）、DMT-NO、N-甲基色胺（NMT）、2-甲基-1,2,3,4-四氢-β-咔啉（2-MTHBC）、色胺（TA）和1,2,3,4-四氢-β-咔啉（THBC）。DMT-NO代谢产生了DMT、NMT、IAA和2-MTHBC。在厌氧孵化条件下，DMT-NO形成这些代谢物的过程被促进...

Studies were conducted using tritiated DMT and DMT-N-oxide (DMT-NO), and metabolites were identified and quantified using thin-layer chromatography and liquid scintillation counting techniques. Metabolite confirmation was obtained by incubation of alpha,alpha,beta,beta-tetradeutero-DMT (DDMT) with whole brain homogenate followed by combined gas chromatographic/mass spectrometric analyses. The metabolites of DMT were identified as indoleacetic acid (IAA), DMT-NO, N-methyltryptamine (NMT), 2-methyl-1,2,3,4-tetrahydro-beta-carboline (2-MTHBC), tryptamine (TA) and 1,2,3,4- tetrahydro-beta-carboline (THBC). DMT-NO was metabolized to give DMT, NMT, IAA and 2-MTHBC. Formation of these metabolites from DMT-NO was stimulated by anaerobic incubation. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

磷酸异烟肼对二甲基色胺（DMT）代谢的影响也进行了研究。异烟肼抑制了从DMT形成IAA的过程，抑制率为83%。然而，在这些条件下，NMT和DMT-NO的形成被抑制了90%。因此，据报道，异烟肼对DMT半衰期的延长和行为效果的增强可能是由于抑制了NMT和DMT-NO的形成，而不是单胺氧化酶的抑制。提出了一个在大脑组织中合成和代谢DMT的循环途径。

... The effects of the monamine oxidase inhibitor iproniazid phosphate on DMT metabolism were also studied. Iproniazid inhibited the formation of IAA from DMT by 83 per cent. However, the formation of NMT and DMT-NO was inhibited by 90 per cent under these conditions. Thus, the reported extension of half-life and potentiation of DMT behavioral effects by iproniazid may be due to inhibition of NMT and DMT-NO formation rather than inhibition of monoamine oxidase. A cyclic pathway for the synthesis and metabolism of DMT in brain tissue is proposed.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

N,N-二甲基色胺（DMT）、哈马里因、哈马拉因和四氢哈马拉因（THH）是在亚马逊圣礼中发现的特征性生物碱，这些圣礼被称为霍萨卡、阿亚瓦斯卡和雅耶。这些饮料的特点是存在这三种哈马拉生物碱，其中哈马里因和哈马拉因可逆地抑制单胺氧化酶A（MAO-A），而四氢哈马拉因则微弱地抑制血清素的摄取。这两种作用共同增加了中枢和周围血清素活性，同时促进了DMT的致幻活性。

N,N-Dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine (THH) are the characteristic alkaloids found in Amazonian sacraments known as hoasca, ayahuasca, and yaje. Such beverages are characterized by the presence of these three harmala alkaloids, where harmine and harmaline reversibly inhibit monoamine oxidase A (MAO-A) while tetrahydroharmine weakly inhibits the uptake of serotonin. Together, both actions increase central and peripheral serotonergic activity while facilitating the psychoactivity of DMT. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

阿片类药物拮抗剂纳洛酮被测试以确定其可能与N,N-二甲基色胺（DMT）的相互作用...在成年雄性Holtzman大鼠中...以递增剂量的DMT（1.0、3.2和10.0 mg/kg）进行i.p.给药，以剂量相关的方式干扰食物奖励的固定比例条杆按压。用行为上无效剂量的纳洛酮（1.0--5.6 mg/kg）预处理（5--10分钟）显著增强了DMT的效果...在大鼠单独注射DMT（10 mg/kg）和用纳洛酮（3.2 mg/kg）预处理5分钟后，通过放射化学分析在大鼠大脑和肝脏中DMT的含量，时间为注射(14)C-DMT后30分钟和90分钟。当对照组DMT大鼠与纳洛酮预处理大鼠进行比较时，大脑或肝脏的(14)C-DMT水平没有显著差异。这些结果似乎排除了纳洛酮通过干扰DMT的代谢作为观察到的行为增强机制的干扰。

The narcotic antagonist naloxone was tested to determine its possible interaction with N,N-dimethyltryptamine (DMT) ... in adult male Holtzman rats ... increasing doses of DMT (1.0, 3.2, and 10.0 mg/kg) were administered i.p. to disrupt food-rewarded fixed ratio bar pressing in a dose related fashion. Pretreatment (5--10 min) with behaviorally ineffective doses of naloxone (1.0--5.6 mg/kg) dramatically enhanced the effects of DMT ... The content of DMT in the brain and liver of rats injected with DMT alone (10 mg/kg) and with a 5 min pretreatment of naloxone (3.2 mg/kg) was determined by radiochemical analysis at 30 and 90 min after (14)C-DMT injection. There was no significant difference for either brain or liver (14)C-DMT levels when control DMT rats were compared with the naloxone pretreated rats. These results seem to rule out interference by naloxone with the metabolism of DMT as a mechanism of the observed behavioral potentiation.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

各种神经安定剂对N, N-二甲基色胺（DMT，3.2毫克/千克）在大兔中引起的发热效果进行了研究。获得了完整的剂量-效应曲线。对抗DMT引起的发热的效果顺序是：甲硫哒嗪大于八氢哒嗪大于或等于羟丙哒嗪大于佩拉哒嗪大于多克洛哒嗪大于米安色林大于洛沙平大于羟哌啶大于氯丙嗪大于匹帕哌隆大于氟奋乃静大于硫噻嗪大于洛哌啶醇大于莫林多酮...结果表明，神经安定剂在对抗DMT的特异性上存在显著差异...这可能是通过不同的神经递质机制（色胺能对肾上腺素能）发挥作用。

The effects of various neuroleptics were studied on N, N-dimethyltryptamine (DMT, 3.2 mg/kg) ... induced hyperthermia in the rabbit. Complete dose-effect curves were obtained. The order of potency for antagonism of DMT-induced hyperthermia was: methiothepin greater than octoclothepin greater than or equal to oxyprothepin greater than perathiepin greater than dokloxythepin greater than mianserine greater than loxapine greater than oxypertine greater than chlorpromazine greater than pipamperone greater than fluphenazine greater than thiothixene greater than haloperidol greater than molindone...The results indicate that neuroleptics differ markedly in their specificity of antagonism of DMT ... which may act through different neurotransmitter mechanisms (tryptaminergic vs. adrenergic).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

对于一个经历“糟糕旅行”或恐慌反应的患者，在一个安静的环境中提供温和的安慰和放松技巧。用安定或咪达唑仑治疗激动或严重焦虑状态。尽管有理论上降低癫痫发作阈值的微小风险，但丁酰苯类药物如氟哌啶醇仍然有效。如果发生癫痫、低体温、横纹肌溶解、高血压和心律失常，则进行治疗。没有特定的解毒剂。安定镇静剂量可以缓解焦虑，而催眠剂量可以诱导睡眠，持续“旅行”的整个过程。/麦角酸二乙基酰胺（LSD）和其他致幻剂/

For a patient with a "bad trip" or panic reaction, provide gentle reassurance and relaxation techniques in a quiet environment. Treat agitation or severe anxiety states with diazepam or midazolam. Butyrophenones such as haloperidol are useful despite a small theoretical risk of lowering seizure threshold. Treat seizures, hypothermia, rhabdomyolysis, hypertension, and cardiac arrhythmias if they occur. There is no specific antidote. Sedating doses of diazepam may alleviate anxiety, and hypnotic doses can induce sleep for the duration of the "trip". /Lysergic Acid Diethylamide (LSD) and other Hallucinogens/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(14)C-DMT在37°C下孵育的大鼠大脑皮层切片中积累。... 积累的大部分(14)C-DMT与细胞质部分相关联。与粗线粒体部分相关联的部分中，54.4%与神经末梢部分相关联。

(14)C-DMT accumulates in rat brain cortical slices incubated at 37 °C. ... Most of the accumulated (14)C-DMT was associated with the cytoplasmic fraction. Of the portion associated with the crude mitochondrial fraction, 54.4% was associated with nerve-ending fraction.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

致幻物质N',N'-二甲色胺及其前体N-甲基色胺在19名正常人的24小时尿样中被发现；平均排泄率分别为386 ng/24小时和856 ng/24小时。两种化合物的尿排泄与年龄、性别、尿量或肌酐无关，也没有观察到任何一致性的昼夜节律。单甲基化和二甲基化化合物的排泄率之间没有相关性。饮食和肠道菌群被排除为尿液中二甲色胺的来源。给4个受试者服用足够的氯化铵以降低尿液的pH值，导致二甲色胺排泄的短暂增加，但N-甲基色胺的排泄率没有一致性的增加。尿液的酸化似乎不是这一结果的决定因素，因为在一个受试者中，通过喂食甲硫氨酸实现了相同的尿pH下降，而二甲色胺的排泄没有增加。

The hallucinogenic substance N',N'-dimethyltryptamine and its precursor N-methyltryptamine were found in 24-hr specimens of urine from 19 normal human subjects; the mean excretion rates were 386 ng 24 hr(-1) and 856 ng 24 hr(-1) respectively. The urinary excretion of both compounds was unrelated to age, sex, urinary volume, or creatinine, nor was any consistent diurnal pattern observed. Rates for the mono and dimethylated compounds were not correlated. Diet and the intestinal flora were excluded as a source of urinary dimethyltryptamine. Administration to 4 subjects of sufficient ammonium chloride to /decrease/ the /pH/ of the urine caused a transient increase in dimethyltryptamine excretion but no consistent increase in the rate for N-methyltryptamine. Acidification of the urine did not appear to be the determining factor in this result since in one subject the same drop in urinary pH was achieved by feeding methionine without any increase in dimethyltryptamine excretion.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

十八名有使用迷幻药物经验的志愿者接受了单次口服封装的冻干ayahusaca（剂量为每公斤体重0.6和0.85毫克的DMT）和安慰剂。Ayahuasca产生了显著的主观效应，在1.5到2小时之间达到峰值，包括感知改变和积极情绪以及激活度的提升。低剂量和高剂量ayahusaca后DMT的Cmax值分别为12.14 ng/mL和17.44 ng/mL。Tmax（中位数）在两种剂量后1.5小时观察到。DMT的Tmax与主观效应的峰值相一致。

... Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 hr, involving perceptual modifications and increases in ratings of positive mood and activation. ...Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/mL and 17.44 ng/mL, respectively. Tmax (median) was observed at 1.5 hr after both doses. The Tmax for DMT coincided with the peak of subjective effects. ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

内源性幻觉剂，N,N-二甲基色胺（DMT），被标记为(11)C，并研究了其在鼠脑中的区域分布。(11)C-DMT在大脑皮层、尾状壳核和杏仁核中的积累较高。当向大鼠注射非常低剂量的(11)C-DMT时，对(11)C-DMT的亚细胞分布的研究揭示了其在富含血清素受体的组分中的特异性定位......

The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with (11)C and its regional distribution in rat brain studied. (11)C-DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of (11)C-DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. ...

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  N,N-二甲基色胺 在 双氧水 作用下， 生成 N,N-Dimethyl-tryptamin-N(b)-oxid
  参考文献：
  名称：

  Piptadenia Alkaloids. Indole Bases of P. peregrina (L.) Benth. and Related Species

  摘要：

  DOI：

  10.1021/ja01627a034
• 作为产物：
  描述：

  2-(1H-吲哚-3-基)-N,N-二甲基乙酰胺 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以92%的产率得到N,N-二甲基色胺
  参考文献：
  名称：

  SPL028：氘代 N,N-二甲基色胺的发现和体外表征

  摘要：

  迷幻剂N , N-二甲基色胺 (DMT) 正在临床开发中，用于治疗重度抑郁症。然而，当通过静脉输注给药时，由于快速清除，其作用是短暂的。在这里，我们描述了 DMT 氘代类似物的合成，目的是延长半衰期并降低清除率，同时保持相似的药理作用。与 DMT 相比，α-碳上氘化程度最高的分子（ N , N -D 2 -二甲基色胺，D 2 -DMT）在肝细胞线粒体部分中表现出最长的半衰期和内在清除率。 D 2 -DMT 的体外受体结合谱与 DMT 相当，对 5-HT 1A 、5-HT 2A和 5-HT 2C受体具有最高亲和力。因此，D 2 -DMT 是考虑进一步评估的首选候选者。

  DOI：

  10.1021/acsmedchemlett.3c00143
• 作为试剂：
  描述：

  B-氯-1,2-苯二酚硼烷 、 1-benzyl-6-chloro-1H-indole 在 aluminum (III) chloride 、 N,N-二甲基色胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以67%的产率得到3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzyl-6-chloro-1H-indole
  参考文献：
  名称：

  [EN] PROCESS FOR THE BORYLATION OF ARENES AND HETEROARYLS
  [FR] PROCÉDÉ DE BORYLATION D'ARÈNES ET D'HÉTÉROARYLES

  摘要：

  这项发明涉及一种新型芳烃和杂环芳烃硼化的过程。本发明还提供了新型硼离子阳，它们作为芳烃或杂环芳烃环上亲电取代的亲电试剂，以及用于制备这些阳离子的方法学。

  公开号：

  WO2012025760A1

文献信息

• 一种制备苯甲酸利扎曲坦的方法
  申请人：四川大学

  公开号：CN103664900B

  公开（公告）日：2016-02-24

  本发明公开了一种新的苯甲酸利扎曲坦的制备方法。该制备方法以色胺为起始原料，经过N，N甲基化，还原，上保护、三氮唑甲基化、脱保护、脱氢，成盐七步反应，得到高纯度的苯甲酸利扎曲坦。该方法的创新之处在于采用了一种全新的方法构建吲哚环，避免了现有路线中使用的fisher吲哚合成法而带来的产品杂质含量高，难于纯化的缺点。该方法的优点为：操作简便，反应条件温和，无昂贵试剂，不需要柱层析纯化，产品纯度高。
• [EN] FACTOR XIa INHIBITORS<br/>[FR] INHIBITEURS DU FACTEUR XIA
  申请人：MERCK SHARP & DOHME

  公开号：WO2015164308A1

  公开（公告）日：2015-10-29

  The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.

  本发明提供了一种化合物(I)及包含一种或多种所述化合物的药物组合物，以及使用所述化合物用于治疗或预防血栓、栓塞、高凝血性或纤维变化的方法。这些化合物是选择性因子XIa抑制剂或因子XIa和血浆激肽原的双重抑制剂。
• A facile procedure for synthesis of 3-[2-(N,N-dialkylamino)ethyl]-3-fluorooxindoles by direct fluorination of N,N-dialkyltryptamines
  作者：Takayuki Seki、Tomoya Fujiwara、Yoshio Takeuchi

  DOI：10.1016/j.jfluchem.2010.12.014

  日期：2011.3

  A practical procedure for the synthesis of 3-fluorooxindole derivatives having basic amine moieties was developed, which involves Selectfluor™-mediated oxidative fluorination of N,N-dialkyltryptamines in the presence of Lewis acid. This procedure was applied to an antimigraine drug, rizatriptan, to afford the corresponding 3-fluorooxindole, which is a potential fluorine-containing drug candidate.

  已开发出一种合成具有碱性胺基团的3-氟羟吲哚衍生物的实用方法，该方法涉及在路易斯酸存在下，Selectfluor TM介导的N，N-二烷基色胺的氧化氟化。将该方法应用于抗偏头痛药物利扎曲普坦（rizatriptan），得到相应的3-氟羟吲哚，其是潜在的含氟药物候选物。
• Ruthenium Pincer Complex Catalyzed Selective Synthesis of C‐3 Alkylated Indoles and Bisindolylmethanes Directly from Indoles and Alcohols
  作者：Nandita Biswas、Rahul Sharma、Dipankar Srimani

  DOI：10.1002/adsc.202000326

  日期：2020.7.29

  catalyst for C‐3 alkylation of 1H‐indoles with various aliphatic primary and secondary alcohols including cyclic alcohols as well as benzylic alcohols. The selective synthesis of bisindolylmethane derivatives is also achieved from the same set of indole and alcohol just by altering the reaction parameters. Furthermore, the sustainable synthesis of C‐3 alkylated indoles directly from 2‐(2‐nitrophenyl)ethan‐1‐ol

  在此，我们介绍了Ru-SNS配合物，该配合物可作为1H-吲哚与各种脂族伯醇和仲醇（包括环状醇以及苄醇）的C-3烷基化的有用催化剂。仅通过改变反应参数，就可以从同一组吲哚和醇中选择性地合成双吲哚基甲烷衍生物。此外，据报道，直接由2-（2-硝基苯基）乙-1-醇和Ru-络合物通过“借用氢”策略催化的醇可持续合成C-3烷基化的吲哚。该协议提供了一种原子经济的可持续途径，可用于访问结构上重要的化合物，如金刚烷，颤敏A和色胺基衍生物。
• Triazole containing indole derivatives
  申请人：Merck Sharp & Dohme Limited

  公开号：US05298520A1

  公开（公告）日：1994-03-29

  A class of substituted imidazole, triazole and tetrazole derivatives are selective agonists of 5-HT.sub.1 -like receptors and are therefore useful in the treatment of clinical conditions, in particular migraine and associated disorders, for which a selective agonist of these receptors is indicated.

  一类取代的咪唑、三唑和四唑衍生物是5-HT.sub.1 -样受体的选择性激动剂，因此在治疗临床疾病中特别有用，尤其是偏头痛和相关的紊乱，对于这些疾病，需要使用这些受体的选择性激动剂。

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