(1R,4S,5'S,6R,6'R,8R,10E,12S,13S,14E,16E,20R,21R,24S)-21,24-dihydroxy-12-[(2R,4S,5S,6S)-5-[(2S,4R,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethyl-6'-propan-2-ylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (1R,4S,5'S,6R,6'R,8R,10E,12S,13S,14E,16E,20R,21R,24S)-21,24-dihydroxy-12-[(2R,4S,5S,6S)-5-[(2S,4R,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethyl-6'-propan-2-ylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one
• 化学式: C₄₇H₇₂O₁₄
• 分子量: 861.1
• InChiKey: VARHUCVRRNANBD-XKYHEAQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  61
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  170
• 氢给体数：
  3
• 氢受体数：
  14

ADMET

代谢

主要在肝脏。伊维菌素及其代谢物几乎全部通过粪便排泄，估计需要12天，给药剂量的不到1%通过尿液排泄。消除途径：伊维菌素在肝脏中代谢，伊维菌素及其代谢物几乎全部通过粪便排泄，估计需要12天，给药剂量的不到1%通过尿液排泄。半衰期：16小时（也有报道称22-28小时）。

Primarily hepatic. Ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1 % of the administered dose excreted in the urine. Route of Elimination: Ivermectin is metabolized in the liver, and ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose excreted in the urine. Half Life: 16 hours (also reported at 22-28 hours)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

伊维菌素选择性地与高亲和力地结合到无脊椎动物肌肉和微丝虫神经细胞中的谷氨酸门控氯离子通道。这种结合导致细胞膜对氯离子的通透性增加，进而导致细胞超极化，致使寄生虫瘫痪和死亡。伊维菌素还被认为是神经递质γ-氨基丁酸（GABA）的激动剂，从而干扰GABA介导的中枢神经系统（CNS）神经突触传递。伊维菌素还可能损害O. volvulus微丝虫的正常子宫内发育，并可能阻止妊娠雌虫子宫中的微丝虫释放。它具有低水溶性，广泛的非特异性结合。它打开了对GABA不敏感的氯通道，降低膜电阻，增加内向电导。

Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells of the microfilaria. This binding causes an increase in the permeability of the cell membrane to chloride ions and results in hyperpolarization of the cell, leading to paralysis and death of the parasite. Ivermectin also is believed to act as an agonist of the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting GABA-mediated central nervous system (CNS) neurosynaptic transmission. Ivermectin may also impair normal intrauterine development of O. volvulus microfilariae and may inhibit their release from the uteri of gravid female worms. It has low solubility in water and extensive non-specific binding. It opens GABA-insensitive chloride channels, reducing membrane resistance and increasing conductance inward. (T10)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

未列入国际癌症研究机构(IARC)的清单。

Not listed by IARC.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

阿维菌素类具有神经毒性，并且对生殖和发育有影响。

Avermectins are neurotoxic and have reproductive and developmental effects. (L1826)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

伊维菌素吸收适中。高脂肪餐可提高吸收率。伊维菌素选择性地与高亲和力结合到无脊椎动物肌肉和微丝虫神经细胞中的谷氨酸门控氯离子通道。这种结合增加了细胞膜对氯离子的通透性，导致细胞超极化，进而导致寄生虫瘫痪和死亡。伊维菌素还被认为是一种神经递质γ-氨基丁酸（GABA）的激动剂，从而干扰GABA介导的中枢神经系统（CNS）神经突触传递。伊维菌素还可能损害O. volvulus微丝虫的正常宫内发育，并可能阻止它们从妊娠雌虫的子宫中释放。它在水中的溶解度很低，具有广泛的非特异性结合。它打开了对GABA不敏感的氯通道，降低膜电阻并增加内向电导。(T10) 主要在肝脏中。伊维菌素及其代谢物几乎全部通过粪便排泄，估计需要12天，给药剂量的不到1%通过尿液排泄。消除途径：伊维菌素在肝脏中代谢，伊维菌素及其代谢物几乎全部通过粪便排泄，估计需要12天，给药剂量的不到1%通过尿液排泄。半衰期：16小时（也有报道称22-28小时）。

Ivermectin is moderately well absorbed. Improved absorption with high fat meal. Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells of the microfilaria. This binding causes an increase in the permeability of the cell membrane to chloride ions and results in hyperpolarization of the cell, leading to paralysis and death of the parasite. Ivermectin also is believed to act as an agonist of the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting GABA-mediated central nervous system (CNS) neurosynaptic transmission. Ivermectin may also impair normal intrauterine development of O. volvulus microfilariae and may inhibit their release from the uteri of gravid female worms. It has low solubility in water and extensive non-specific binding. It opens GABA-insensitive chloride channels, reducing membrane resistance and increasing conductance inward. (T10) Primarily hepatic. Ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1 % of the administered dose excreted in the urine. Route of Elimination: Ivermectin is metabolized in the liver, and ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose excreted in the urine. Half Life: 16 hours (also reported at 22-28 hours)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

阿维菌素会导致皮肤和眼睛刺激、中枢神经系统抑制（不协调、震颤、乏力、兴奋、瞳孔扩大、昏迷）、呕吐、惊厥和/或震颤，以及在高剂量下的呼吸衰竭。（L1826）不良反应包括肌肉或关节疼痛、头晕、发热、头痛、皮疹和心跳加速。

Avermectins cause irritation of skin and eyes, central nervous system depression (incoordination, tremors, lethargy, excitation, pupil dilation, coma), vomiting, convulsions and/or tremors, and respiratory failure at high doses. (L1826) Adverse effects include muscle or joint pain, dizziness, fever, headache, skin rash, fast heartbeat.

来源:Toxin and Toxin Target Database (T3DB)

文献信息

• METHODS OF REDUCING NEMATODE DAMAGE
  申请人：Syngenta Participations AG

  公开号：EP1765079A1

  公开（公告）日：2007-03-28
• METHOD FOR THE PROTECTION OF TREES
  申请人：The Texas A&M University System

  公开号：EP1863496A2

  公开（公告）日：2007-12-12
• [EN] METHODS OF REDUCING NEMATODE DAMAGE<br/>[FR] PROCEDES DE REDUCTION DE DOMMAGE CAUSE PAR DES NEMATODES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2005120232A1

  公开（公告）日：2005-12-22

  A method of reducing damage to plant propagation material and plant organs which grow at a later time by a representative of the class Nematode, which method comprises (I) treating the propagation material with (A) a chelating agent, and optionally (B) a macrocyclic lactone compound or another pesticide, before the material is sown or planted, or (II) applying (A) a chelating agent, and optionally (B) a macrocyclic lactone compound or another pesticide, to the locus of the material or the treated material defined in (I) before its planting, and/or at its planting and/or during its growth.
• [EN] METHOD FOR THE PROTECTION OF TREES<br/>[FR] METHODE POUR PROTEGER DES ARBRES
  申请人：TEXAS A & M UNIV SYS

  公开号：WO2006102285A2

  公开（公告）日：2006-09-28

  [EN] The present invention provides a method for the prevention/treatment of bark beetle and/or wood borer infestation of trees comprising treatment of the tree with a composition comprising a macroyclic lactone.
  [FR] L'invention concerne une méthode pour prévenir/traiter une infestation de scolytes sur des arbres. Cette méthode consiste à traiter l'arbre à l'aide d'une composition comprenant un lactone macrocyclique.
• [EN] RECOMBINANT MICROORGANISM PRODUCING MILBEMYCIN, AND MILBEMYCIN PRODUCTION USING SAME<br/>[FR] MICRO-ORGANISME RECOMBINÉ PRODUISANT DE LA MILBÉMYCINE, ET PRODUCTION DE MILBÉMYCINE À L'AIDE DE CELUI-CI<br/>[KO] 밀베마이신을 생산하는 재조합 미생물 및 이를 이용한 밀베마이신 생산
  申请人：FARM HANNONG CO LTD

  公开号：WO2017052232A1

  公开（公告）日：2017-03-30

  밀베마이신을 생산하는 재조합 스트렙토마이세스 아베르미틸리스 (Streptomyces avermitilis) 균주 및 이를 이용한 밀베마이신 생산 방법이 제공된다.