Liver test abnormalities have been reported to occur in up to 16% of patients being treated with tricyclic antidepressants, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Rare instances of clinically apparent acute liver injury have been reported due to doxepin, but the number of cases have been too few to characterize the clinical features. Recurrent jaundice and marked aminotransferase elevations with repeated exposures to doxepin has been reported. Most cases have been mild and deaths from acute liver failure or chronic injury have not been reported.
◉ Summary of Use during Lactation:Because of its sedating potential, active metabolite, presence in infant serum, two reports of adverse effects in breastfed infants, and only one report of use without apparent adverse reactions, doxepin is a poor choice and other agents are preferred, especially while nursing a newborn or preterm infant. A safety scoring system finds doxepin to be not recommended during breastfeeding.
Maternal use of topical doxepin cream is unlikely to pose a problem for a breastfed infant as long as it is applied away from the breasts so that the infant cannot ingest the drug directly.
◉ Effects in Breastfed Infants:One infant was breastfed (extent not stated) over a 2-month period during maternal use of doxepin 150 mg at bedtime, beginning at 30 days postpartum. The infant experienced no apparent adverse reactions.
One infant had an adverse reaction that was probably caused by doxepin in breastmilk. An 8-week old breastfed infant was found pale, limp, somnolent and almost not breathing 4 days after the maternal dosage had been increased from 10 mg daily to 25 mg three times daily. The infant returned to normal 24 hours after discontinuing breastfeeding.
A 9-day-old breastfed infant had poor sucking and swallowing, hypotonia, vomiting, and weight loss. The reaction was probably caused by doxepin in breastmilk. The infant's mother was taking 35 mg of doxepin at bedtime daily.
◉ Effects on Lactation and Breastmilk:An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge. The antidepressants used by the mothers were not specified.
A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis. None of the mothers were taking doxepin.
In a study of 80,882 Norwegian mother-infant pairs from 1999 to 2008, new postpartum antidepressant use was reported by 392 women and 201 reported that they continued antidepressants from pregnancy. Compared with the unexposed comparison group, late pregnancy antidepressant use was associated with a 7% reduced likelihood of breastfeeding initiation, but with no effect on breastfeeding duration or exclusivity. Compared with the unexposed comparison group, new or restarted antidepressant use was associated with a 63% reduced likelihood of predominant, and a 51% reduced likelihood of any breastfeeding at 6 months, as well as a 2.6-fold increased risk of abrupt breastfeeding discontinuation. Specific antidepressants were not mentioned.
◈ What is doxepin?
Doxepin is a tricyclic antidepressant that has been used to treat alcoholism, anxiety, depression, and insomnia (trouble sleeping). As a cream, it has been used for short-term treatment of itchiness. Some brand names include Quitaxon®, Prudoxin®, Silenor®, Sinequan®, and Zonalon®. It is also sold as a combination drug with another medication called levomenthol under the brand name Doxure®.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.
◈ I take doxepin. Can it make it harder for me to get pregnant?
It is not known if doxepin can make it harder to get pregnant.
◈ Does taking doxepin increase the chance for miscarriage?
Miscarriage is common and can occur in any pregnancy for many different reasons. Based on the studies reviewed, it is not known if doxepin increases the chance for miscarriage.
◈ Does taking doxepin increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Based on the studies reviewed, it is not known if doxepin increases the chance of birth defects. Data from animal studies does not suggest an increased chance for birth defects. In a case series looking at 8 human pregnancies, there were no birth defects reported.
◈ Does taking doxepin in pregnancy increase the chance of other pregnancy-related problems?
Based on the studies reviewed, it is not known if doxepin can cause other pregnancy-related problems, such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth).
◈ I need to take doxepin throughout my entire pregnancy. Will it cause withdrawal symptoms in my baby after birth?
The use of tricyclic antidepressants during pregnancy can cause temporary symptoms in newborns soon after birth. These symptoms are sometimes referred to as withdrawal. Symptoms reported with other tricyclic antidepressants include jitteriness, vomiting, crying, fussiness, changes in sleep patterns, tremors, trouble with eating and/or regulating body temperature. In most cases these symptoms were mild and went away on their own within a week or two after birth. Not all babies exposed to tricyclic antidepressants will have these symptoms. It is not known if taking doxepin during pregnancy can cause symptoms in newborns. However, it is important that your healthcare providers know you are taking doxepin so that if symptoms occur your baby can get the care that is best for them.
◈ Does taking doxepin in pregnancy affect future behavior or learning for the child?
Based on the studies reviewed, it is not known if doxepin increases the chance for behavior or learning issues.
◈ Breastfeeding while taking doxepin:
Doxepin gets into breastmilk in small amounts. Information about the use of doxepin while breastfeeding is limited. There are two case reports of respiratory depression (trouble breathing) in babies who were exposed to doxepin through breastmilk. If you suspect the baby has any symptoms (trouble breathing, is not gaining weight, has constipation, or is very sleepy), contact the child’s healthcare provider. Be sure to talk to your healthcare provider about all of your breastfeeding questions.
◈ If a male takes doxepin, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Based on the studies reviewed, it is not known if doxepin could affect fertility or increase the chance of birth defects above the background risk. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.A pregnancy registry for psychiatric medications, including this one, has been organized at the Massachusetts General Hospital. Contact the registry at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.
来源:Mother To Baby Fact Sheets
毒理性
相互作用
/盐酸多塞平/...可能会增强酒精的抑制作用。
/DOXEPIN/...MAY...POTENTIATE THE DEPRESSANT EFFECT OF ALCOHOL. /HYDROCHLORIDE/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
相互作用
抑制盐酸胍乙啶的抗高血压效果的剂量可以是每日200-300毫克。/氢氯酸盐/
INHIBITION OF THE ANTIHYPERTENSIVE EFFECT OF GUANETHIDINE CAN OCCUR WITH DOSES OF 200-300 MG/DAY. /HYDROCHLORIDE/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
多塞平具有...对葡萄膜黑色素有特殊的亲和力...同样...在体内和体外都可以被眼黑色素结合。
/DOXEPIN HAS/...A PECULIAR AFFINITY FOR UVEAL MELANIN...ALSO...BOUND BY OCULAR MELANIN BOTH IN VIVO & IN VITRO.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
口服75毫克盐酸多塞平后，估计首次通过代谢的范围为55-87%，假设完全吸收。
AFTER HUMAN ORAL DOSE 75 MG DOXEPIN-HCL, EST 1ST-PASS METAB RANGED FROM 55-87% OF ORAL DOSE ASSUMING COMPLETE ABSORPTION.
The pharmacokinetics of doxepin have not been extensively studied, but the drug is well absorbed from the GI tract in animals. Peak plasma concentrations occur within 2 hours after oral administration of the drug.
Limited data indicate that doxepin and its active N-demethylated metabolite are distributed into milk in concentrations reportedly ranging from about 30-140% and 10-115%, respectively, of those in maternal serum and that substantial concentrations of the active metabolite have been detected in the serum and urine of nursing infants whose mothers were receiving 75-150 mg daily.
[EN] METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHYLOXAZOLES ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
申请人：MERCK SHARP & DOHME
公开号：WO2016089721A1
公开（公告）日：2016-06-09
The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
Leukotriene A4 hydrolase (LTA4H) inhibitors, compositions containing them, and methods of use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation.
Heterobicyclic compounds of Formula (I):
or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Huntington's Disease, and the like.
Formula (I)的杂环化合物：
或其药用可接受的盐、互变异构体或立体异构体，如规范中所定义，并含有它们的组合物，以及制备这种化合物的方法。本文还提供了通过抑制PDE10来治疗由此可治疗的疾病或疾病的方法，如肥胖症、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症、亨廷顿病等。
[EN] IMIDAZOLIUM REAGENT FOR MASS SPECTROMETRY<br/>[FR] RÉACTIF D'IMIDAZOLIUM POUR SPECTROMÉTRIE DE MASSE
申请人：HOFFMANN LA ROCHE
公开号：WO2021234004A1
公开（公告）日：2021-11-25
The present invention relates to compounds which are suitable to be used in mass spectrometry as well as methods of mass spectrometric determination of analyte molecules using said compounds.
本发明涉及适用于质谱的化合物，以及利用该化合物进行分析物分子的质谱测定方法。
[EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
申请人：MERCK SHARP & DOHME
公开号：WO2011149801A1
公开（公告）日：2011-12-01
The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
