(1S,9S)-1,13-dimethyl-10-(3-methylbut-2-enyl)-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-ol

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 6,7-苯并吗啡烷
• 英文名称: (1S,9S)-1,13-dimethyl-10-(3-methylbut-2-enyl)-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-ol
• 化学式: C₁₉H₂₇NO
• 分子量: 285.4
• InChiKey: VOKSWYLNZZRQPF-SQJZIBIZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

戊唑辛产生1,2,3,4,5,6-六氢-8-羟基-α,6(等),11(轴)-三甲基-2,6-甲烷-3-苯并氮杂环-3-顺式-2-丁烯-1-醇和1,2,3,4,5,6-六氢-8-羟基-α,6(等),11(轴)-三甲基-2,6-甲烷-3-苯并氮杂环-3-反式-2-丁烯-1-醇在猴子和老鼠体内。/来自表格/

PENTAZOCINE YIELDS 1,2,3,4,5,6-HEXAHYDRO-8-HYDROXY- ALPHA,6(EQ),11(AX)-TRIMETHYL-2,6-METHANO-3-BENZAZOCINE-3-CIS-2-BUTEN-1-OL & 1,2,3,4,5,6-HEXAHYDRO-8-HYDROXY-ALPHA,6(EQ),11(AX)- TRIMETHYL-2,6-METHANO-3-BENZAZOCINE-3-TRANS-2-BUTEN-1-OL IN MONKEY & MOUSE. /FROM TABLE/

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 喷他佐辛的代谢速率在吸烟者与非吸烟者之间有所不同。

... RATE OF METABOLISM OF PENTAZOCINE HAS BEEN SHOWN TO DIFFER /BETWEEN/ SMOKERS & NON-SMOKERS.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠口服喷他佐辛后，尿液中发现的主要是喷他佐辛及其葡萄糖醛酸苷结合物。尽管从尿液中提取并鉴定了八种代谢物，但它们的量很小，表明了芳香环的羟基化和甲氧基化，以及一些二甲基丙烯侧链的氧化。

IN THE RAT, AFTER ORAL ADMIN OF PENTAZOCINE, MAINLY PENTAZOCINE & ITS GLUCURONIDE CONJUGATES WERE FOUND IN URINE. ALTHOUGH EIGHT METABOLITES WERE EXTRACTED FROM URINE & CHARACTERIZED ... THE AMOUNTS WERE SMALL AND INDICATED HYDROXYLATION AND METHOXYLATION OF THE AROMATIC RING, WITH SOME OXIDN OF THE DIMETHYLALLYL SIDE-CHAIN.

来源:Hazardous Substances Data Bank (HSDB)

代谢

戊唑辛在肝脏中代谢，主要是通过氧化甲基烷基侧链末端的甲基团，形成醇和羧酸代谢物；葡萄糖苷酸结合也会发生。

Pentazocine is metabolized in the liver, mainly by oxidation of the terminal methyl groups of the dimethyl alkyl side chain to form alcoholic and carboxylic acid metabolites; glucuronide conjugation also occurs.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用总结：目前没有关于哺乳期间使用喷他佐辛的信息。哺乳期母亲口服阿片类药物可能会导致婴儿昏睡，严重的中枢神经系统抑制。新生儿似乎对即使是小剂量的麻醉性镇痛药的效果也非常敏感。一旦母亲的乳汁开始分泌，最好使用非麻醉性镇痛药来控制疼痛，并将母亲摄入喷他佐辛的量限制在2到3天内的低剂量，并密切监测婴儿。如果宝宝表现出过度嗜睡（比平时更甚）、哺乳困难、呼吸困难或无力，应立即联系医生。在哺乳期间，首选其他药物而不是喷他佐辛。 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 对泌乳和母乳的影响：喷他佐辛可以提高血清催乳素水平。然而，对于已经建立泌乳的母亲来说，催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:No information is available on the use of pentazocine during breastfeeding. Maternal use of oral opioids during breastfeeding can cause infant drowsiness, and severe central nervous system depression. Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of pentazocine to 2 to 3 days at a low dosage with close infant monitoring. If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately. Other agents are preferred over pentazocine during breastfeeding. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Pentazocine can increase serum prolactin. However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

...可能增强中枢神经系统抑制剂的效果...

... MAY POTENTIATE /THE DEPRESSANT EFFECTS OF/ CNS DEPRESSANTS ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

戊唑辛微弱地（约为纳洛芬的1/50）拮抗吗啡、美沙酮和芬太尼的镇痛效果。它还能部分逆转由吗啡和美沙酮引起的心血管、呼吸和行为的抑制。

PENTAZOCINE WEAKLY (ABOUT 1/50 THAT OF NALORPHINE) ANTAGONIZES THE ANALGESIC EFFECT OF MORPHINE, MEPERIDINE, AND PHENAZOCINE. IT ALSO PRODUCES INCOMPLETE REVERSAL OF THE CARDIOVASCULAR, RESP, AND BEHAVIORAL DEPRESSION INDUCED BY MORPHINE AND MEPERIDINE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

研究了戊唑辛对幼年大鼠4周内的生长抑制作用。以体重作为评估生长速度的指标。单独使用戊唑辛从治疗的第二周到第四周显著抑制了生长。多巴胺拮抗剂美托洛尔几乎完全阻止了戊唑辛的生长抑制作用。L-多巴与戊唑辛联合使用在第一周产生了显著的生长抑制作用，但随后这种效果与单独使用戊唑辛相比显著减弱。

GROWTH INHIBITORY EFFECT OF PENTAZOCINE WAS STUDIED IN YOUNG RATS FOR A DURATION OF 4 WK. BODY WEIGHT WAS TAKEN AS A MEASURE FOR THE ASSESSMENT OF GROWTH RATE. PENTAZOCINE ALONE MARKEDLY INHIBITED THE GROWTH FROM THE SECOND TO FOURTH WEEK OF TREATMENT. /THE/ DOPAMINE ANTAGONIST METOCLOPRAMIDE ALMOST COMPLETELY PREVENTED THE GROWTH INHIBITORY EFFECT OF PENTAZOCINE. COMBINATION OF L-DOPA WITH PENTAZOCINE PRODUCED A SIGNIFICANT GROWTH INHIBITION IN THE FIRST WEEK BUT SUBSEQUENTLY THIS EFFECT WAS SIGNIFICANTLY LESS MARKED AS COMPARED TO THAT OF PENTAZOCINE ALONE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

对新生儿行为的评估显示，在整个怀孕期间使用盐酸喷他佐辛和盐酸三乙撑胺（T's & Blue's）的母亲的婴儿表现出交互缺陷和类似于海洛因成瘾新生儿的戒断症状。/盐酸喷他佐辛 & 盐酸三乙撑胺/

AN EVALUATION OF NEONATAL BEHAVIOR REVEALED THAT INFANTS OF MOTHERS WHO USED PENTAZOCINE HYDROCHLORIDE & TRIPELENNAMINE HYDROCHLORIDE (T'S & BLUE'S) THROUGHOUT PREGNANCY DEMONSTRATED INTERACTIVE DEFICITS & WITHDRAWAL SIMILAR TO METHADONE ADDICTED NEWBORNS. /PENTAZOCINE HYDROCHLORIDE & TRIPELENNAMINE HYDROCHLORIDE/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

单次给药后，可以在尿液中检测到喷他佐辛及其代谢物的痕迹量，持续数天。/喷他佐辛乳酸盐/

TRACE AMT OF PENTAZOCINE AND ITS METABOLITES CAN BE DETECTED IN URINE FOR SEVERAL DAYS AFTER A SINGLE ADMIN OF THE DRUG. /PENTAZOCINE LACTATE/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

剂量的剂量、血液浓度和尿排泄速率在口服和直肠给药后低于静脉给药后的人。即使在使用直肠给药后，粪便回收率也很低，这表明可用性降低可能是由于吸收过程中的肠道或肝脏清除。

... DOSE FOR DOSE, BLOOD CONCN & URINARY EXCRETION RATES OF PENTAZOCINE WERE LOWER AFTER ORAL & RECTAL DOSAGE THAN AFTER IV DOSAGE TO MAN. FECAL RECOVERY WAS LOW EVEN AFTER RECTAL DOSING, SUGGESTING THAT REDUCED AVAILABILITY MAY BE DUE TO INTESTINAL OR HEPATIC CLEARANCE DURING ABSORPTION.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

戊唑辛迅速从血浆进入脑脊液，脑脊液与血浆的比值在静脉给药后2到3小时内从0.2变化到0.6，与血浆中游离戊唑辛与总戊唑辛的比值相吻合。

PENTAZOCINE ENTERS THE CSF RAPIDLY FROM PLASMA AND CSF:PLASMA RATIOS, WHICH VARIED FROM 0.2 TO 0.6 BETWEEN 2 AND 3 HR AFTER IV DOSES, AGREED WELL WITH THE RATIO OF UNBOUND:TOTAL PENTAZOCINE IN PLASMA.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

戊唑辛通过各种给药途径都能很好地吸收，但个体间的差异较大。口服给药的生物利用度为18.4% +/- 7.8%；这种减少是由于首次通过代谢。

PENTAZOCINE IS WELL ABSORBED BY ALL ROUTES OF ADMIN, BUT THERE IS CONSIDERABLE INDIVIDUAL VARIATION. BIOAVAILABILITY AFTER ORAL ADMIN IS 18.4% +/- 7.8%; THE REDUCTION IS DUE TO FIRST-PASS METABOLISM.

来源:Hazardous Substances Data Bank (HSDB)