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.
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.
◉ 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抑制作用 ...
... MAY POTENTIATE /THE DEPRESSANT EFFECTS OF/ CNS DEPRESSANTS ...
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.
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.
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/
... 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.
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.
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.
Synthesis and characterization of [125I]3′-(−)-iodopentazocine, a selective σ1 receptor ligand
摘要：
Pentazocine is a potent ligand at both opioid and sigma receptors, but with opposite stereoselectivities. Whereas(-)-pentazocine has high affinity for a number of opioid receptors, (+)-pentazocine labels sigma(1) receptors. Iodination of(-)-pentazocine at the 3'-position reverses its selectivity for opioid and sigma(1) receptors. 3'-(-)-Iodopentazocine competes at sigma(1) receptor binding sites with a K-i value of 8 nM, compared to approximately 40 nM for(-)-pentazocine. 3'-(-)-Iodopentazocine also has lost its affinity for opioid receptors. In contrast, iodination of(+)-pentazocine lowers its affinity at sigma(1) receptors. Synthesis of [I-125]3'-(-)-iodopentazocine is readily performed with incorporations of up to 80%. Binding is of high affinity and shows the selectivity anticipated for a sigma(1) receptor-selective ligand. Exposing membranes prebound with [I-125]3'-(-)-iodopentazocine to ultraviolet light can covalently couple the ligand into the membranes. Polyacrylamide gel electrophoresis reveals a major band at about 25 kDa and a minor one at about 20 kDa, indicating photolabeling of sigma(1) receptors with minor incorporation into sigma(2) sites.
[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.
[EN] QUINAZOLINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] DÉRIVÉS DE QUINAZOLINE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
申请人：UNIV EMORY
公开号：WO2013181135A1
公开（公告）日：2013-12-05
The disclosure relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidases (Nox enzymes) and/or myeloperoxidase.
[EN] AZOLE COMPOUNDS AS PIM INHIBITORS<br/>[FR] COMPOSÉS D'AZOLE UTILISÉS EN TANT QU'INHIBITEURS DES PIM
申请人：AMGEN INC
公开号：WO2012129338A1
公开（公告）日：2012-09-27
The invention relates to bicyclic compounds of formulas I and Ia, and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.
[EN] COMBINATIONS OF INHIBITORS OF IRAK4 WITH INHIBITORS OF BTK<br/>[FR] COMBINAISONS D'INHIBITEURS DE L'IRAK4 À L'AIDE D'INHIBITEURS DE LA BTK
申请人：BAYER PHARMA AG
公开号：WO2016174183A1
公开（公告）日：2016-11-03
The present application relates to novel combinations of at least two components, component A and component B: · component A is an IRAK4-inhibiting compound of the formula (I) as defined herein, or a diastereomer, an enantiomer, a metabolite, a salt, a solvate or a solvate of a salt thereof; · component B is a BTK-inhibiting compound, or a pharmaceutically acceptable salt thereof; and, optionally, · one or more components C which are pharmaceutical products; in which one or two of the above-defined compounds A and B are optionally present in pharmaceutical formulations ready for simultaneous, separate or sequential administration, for treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of endometriosis, lymphoma, macular degeneration, COPD, neoplastic disorders and psoriasis.
A pharmaceutically active inventive compound comprises two independently active analgesic moieties covalently conjoined through a physiologically labile linker. A preferred embodiment comprises an opioid, such as morphine, covalently linked to at least one analgesic compound selected from the group consisting of an opioid or a non-opioid compound through a physiologically labile linker. Suitable covalent linkers are covalently bonded to the two independently active analgesic compounds through one or more lactone, lactam, or sulfonamido linkages. Suitable linkers include endogenous carboxylate, amido, and sulfonamido moieties, and exogenous moieties that form the aforementioned lactone, lactam or sulfonamido linkages.
