Antitussive Agents
Papaver
Noscapine hydrochloride disrupts the mitotic spindle in mammalian cells and induces aneuploidy as well as polyploidy in cultured human lymphocytes. (1/42)
Noscapine hydrochloride is a centrally acting antitussive opium derivative widely used in cough suppressants. Recent studies have reported that noscapine is a potent inducer of polyploidy but not of aneuploidy in vitro. To obtain more comprehensive information about the cytogenetic effects of this compound, we treated cultured human lymphocytes (HPL) and Chinese hamster ovary (CHO) cells with various concentrations of noscapine hydrochloride. Using a differential staining technique noscapine was shown to disrupt the mitotic spindle at concentrations < 5 micrograms/ml in both cell types. The use of multicolor fluorescence in situ hybridization (FISH) on noscapine-treated human lymphocytes showed a dose-dependent induction of hyperdiploidy of chromosome 1 but not of chromosomal breakage in the 1cen-q12 region under in vitro conditions, indicating that noscapine is specifically inducing numerical chromosomal aberrations. FISH with probes targeting different chromosomes revealed that noscapine is capable of inducing both polyploidy and true hyperdiploidy. Our results show that noscapine, by disrupting the function of the mitotic spindle, has the ability to induce aneuploidy and not uniquely polyploidy as previously reported. By using these types of molecular cytogenetic techniques, it should be possible to evaluate the ability of noscapine to induce aneuploidy in the upper intestinal tract in vivo. (+info)Peripheral T-cell lymphoma with aberrant expression of CD79a and CD20: a diagnostic pitfall. (2/42)
Immunohistochemical studies are increasingly used for the routine diagnosis of lymphomas as it is widely accepted that lymphomas of different cell lineages vary in their prognosis and response to therapy. A case of peripheral T-cell lymphoma with aberrant expression of B-cell-associated antigens L-26 (CD20) and mb-1 (CD 79a) is described. The disease pursued an aggressive clinical course, and the patient died of disease 6 weeks after presentation. Immunohistochemical studies demonstrated expression of both T- and B-cell-associated antigens, including CD3, CD8, CD43, TIA-1, CD20, and CD79a. Other markers expressed by the tumor cells included CD56 and S-100. Of interest, betaF-1 staining for the beta chain of T-cell receptor (TCR) complex was positive in the small admixed T lymphocytes but was negative in the tumor cells, raising the possibility of a gamma/delta T-cell lymphoma. Molecular studies by polymerase chain reaction (PCR) demonstrated clonal TCR-gamma chain gene rearrangement without evidence for a clonal rearrangement of the immunoglobulin heavy chain gene. PCR for HHV-8 related sequences was negative. Mb-1 is an IgM-associated protein that was thought to be restricted to normal and neoplastic B cells. Although its coexpression has been reported in up to 10% cases of precursor T-cell lymphoblastic lymphoma, the coexpression of both CD20 and CD79a has not been described in mature T-cell malignancies. Biphenotypic lymphomas associated with HHV-8 have been reported in immunodeficiency, but no evidence of immune deficiency was identified, and studies for EBV and HHV-8 were negative. This case illustrates that no marker has absolute lineage specificity and that immunophenotypic studies should always be performed with panels of monoclonal antibodies. Moreover, cases with ambiguous phenotypes may require genotypic studies for precise lineage assignment. (+info)Sustained activation of p34(cdc2) is required for noscapine-induced apoptosis. (3/42)
Mitotic arrest and subsequent apoptosis has been observed in many types of cells treated with anti-microtubule agents. However, the molecular mechanisms underlying the two events as well as their relationship are not well understood; on the contrary, there has been increasing evidence indicating that anti-microtubule agents might induce apoptosis via signaling pathways independent of mitosis. In this study, we found that apoptosis induced by noscapine, an anti-microtubule drug previously shown to cause both mitotic arrest and apoptotic cell death, was blocked by inhibiting p34(cdc2) activity with olomoucine in FM3A murine mammary carcinoma cells or by reducing the level and activity of p34(cdc2) in a mutant cell line FT210 derived from FM3A. Furthermore, transfection of the mutant FT210 cells with wild-type p34(cdc2) restored their ability to undergo mitotic arrest and then apoptosis in response to noscapine. Thus, we conclude that sustained activation of the p34(cdc2) kinase during mitotic arrest is required for subsequent apoptosis induced by noscapine, establishing a link between the two events. (+info)Minor alteration of microtubule dynamics causes loss of tension across kinetochore pairs and activates the spindle checkpoint. (4/42)
We have previously identified the opium alkaloid noscapine as a microtubule interacting agent that binds stoichiometrically to tubulin and alters its conformation. Here we show that, unlike many other microtubule inhibitors, noscapine does not significantly promote or inhibit microtubule polymerization. Instead, it alters the steady-state dynamics of microtubule assembly, primarily by increasing the amount of time that the microtubules spend in an attenuated (pause) state. Further studies reveal that even at high concentrations, noscapine does not alter the tubulin polymer/monomer ratio in HeLa cells. Cells treated with noscapine arrest at mitosis with nearly normal bipolar spindles. Strikingly, although most of the chromosomes in these cells are aligned at the metaphase plate, the rest remain near the spindle poles, both of which exhibit loss of tension across kinetochore pairs. Furthermore, levels of the spindle checkpoint proteins Mad2, Bub1, and BubR1 decrease by 138-, 3.7-, and 3.9-fold, respectively, at the kinetochore region upon chromosome alignment. Our results thus suggest that an exquisite control of microtubule dynamics is required for kinetochore tension generation and chromosome alignment during mitosis. Our data also support the idea that Mad2 and Bub1/BubR1 respond to kinetochore-microtubule attachment and/or tension to different degrees. (+info)Noscapine alters microtubule dynamics in living cells and inhibits the progression of melanoma. (5/42)
Cellular microtubules, polymers of tubulin, alternate relentlessly between phases of growth and shortening. We now show that noscapine, a tubulin-binding agent, increases the time that cellular microtubules spend idle in a paused state. As a result, most mammalian cell types observed arrest in mitosis in the presence of noscapine. We demonstrate that noscapine-treated murine melanoma B16LS9 cells do not arrest in mitosis but rather become polyploid followed by cell death, whereas primary melanocytes reversibly arrest in mitosis and resume a normal cell cycle after noscapine removal. Furthermore, in a syngeneic murine model of established s.c. melanoma, noscapine treatment resulted in an 85% inhibition of tumor volume on day 17 when delivered by gavage compared with untreated animals (PPaclitaxel-resistant human ovarian cancer cells undergo c-Jun NH2-terminal kinase-mediated apoptosis in response to noscapine. (6/42)
We have previously discovered the opium alkaloid noscapine as a microtubule interacting agent that binds to tubulin, alters the dynamics of microtubule assembly, and arrests mammalian cells at mitosis (Ye, K., Ke, Y., Keshava, N., Shanks, J., Kapp, J. A., Tekmal, R. R., Petros, J., and Joshi, H. C. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 1601-1606; Ye, K., Zhou, J., Landen, J. W., Bradbury, E. M., and Joshi, H. C. (2001) J. Biol. Chem. 276, 46697-46700; Zhou, J., Panda, D., Landen, J. W., Wilson, L., and Joshi, H. C. (2002) J. Biol. Chem. 277, 17200-17208). Here we show that noscapine does not compete with paclitaxel for tubulin binding and can efficiently inhibit the proliferation of both paclitaxel-sensitive and paclitaxel-resistant human ovarian carcinoma cells (i.e. the parental cell line 1A9 and two derivative cell lines, 1A9PTX10 and 1A9PTX22, which harbor beta-tubulin mutations that impair paclitaxel-tubulin interaction (Giannakakou, P., Sackett, D. L., Kang, Y. K., Zhan, Z., Buters, J. T., Fojo, T., and Poruchynsky, M. S. (1997) J. Biol. Chem. 272, 17118-17125). Strikingly, these cells undergo apoptotic death upon noscapine treatment, accompanied by activation of the c-Jun NH(2)-terminal kinases (JNK). Furthermore, inhibition of JNK activity by treatment with antisense oligonucleotide or transfection with dominant-negative JNK blocks noscapine-induced apoptosis. These findings thus indicate a great potential for noscapine in the treatment of paclitaxel-resistant human cancers. In addition, our results suggest that the JNK pathway plays an essential role in microtubule inhibitor-induced apoptosis. (+info)Brominated derivatives of noscapine are potent microtubule-interfering agents that perturb mitosis and inhibit cell proliferation. (7/42)
Noscapine, a microtubule-interfering agent, has been shown to arrest mitosis, to induce apoptosis, and to have potent antitumor activity. We report herein that two brominated derivatives of noscapine, 5-bromonoscapine (5-Br-nosc) and reduced 5-bromonoscapine (Rd 5-Br-nosc), have higher tubulin binding activity than noscapine and affect tubulin polymerization differently from noscapine. In addition, they are able to arrest cell cycle progression at mitosis at concentrations much lower than noscapine. Interestingly, whereas noscapine-arrested cells have nearly normal bipolar spindles, cells arrested by 5-Br-nosc and Rd 5-Br-nosc form multipolar spindles. Nevertheless, noscapine and the two derivatives all affect the attachment of chromosomes to spindle microtubules and they impair the tension across paired kinetochores to similar degrees. 5-Br-nosc and Rd 5-Br-nosc are also more active than noscapine in inhibiting the proliferation of various human cancer cells, including those that are resistant to paclitaxel and epothilone. Our results thus indicate a great potential for the use of 5-Br-nosc and Rd 5-Br-nosc both as biological tools for studying microtubule-mediated processes and as chemotherapeutic agents for the treatment of human cancers. (+info)Noscapine hydrochloride-induced numerical aberrations in cultured human lymphocytes: a comparison of FISH detection methods and multiple end-points. (8/42)
The cytokinesis block in vitro micronucleus (MN) assay in combination with CREST staining and fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes allows mechanistic information on the induction of numerical chromosomal aberrations to be obtained through a rapid and simple microscopic analysis. These techniques can now be used to investigate relationships between the induction of chromosomal loss, non-disjunction and polyploidy by aneuploidy-inducing agents. In the present study, we treated 72 h cultured lymphocytes for the last 24 h of culture with various concentrations of the cough medicine noscapine hydrochloride (NOS) (3.9-120 micro g/ml) in the presence of either cytochalasin B (CYB) (3 micro g/ml) or 5-bromo-2'-deoxyuridine (BrdU) (1 micro M). Using the CREST staining modified MN assay in the CYB-treated cultures, we detected significant increases in CREST-positive but not CREST-negative MN in both binucleated and, to a lesser extent, mononucleated cells, demonstrating the ability of this compound to induce chromosomal loss. In addition, using FISH with chromosome 1- and 9-specific classical satellite probes, a significant induction of chromosomal non-disjunction in the binucleated lymphocytes and polyploidy in the mononucleated lymphocytes was seen, indicating that polyploidy induced by NOS may occur without progression through a normal anaphase and/or telophase. In the BrdU-treated cultures, a dose-dependent induction of hypodiploidy, hyperdiploidy and polyploidy was observed using FISH with a chromosome 9-specific alpha-satellite probe in the labeled cells. By comparison, in the unlabeled non-cycling cells, only a slight increase in hyperdiploidy/polyploidy but not hypodiploidy was seen. A comparison of the effects seen at different concentrations shows that at the lower effective concentrations, all three types of numerical aberrations, chromosomal loss, non-disjunction and polyploidy, contributed to the numerical aberrations seen, whereas at the highest concentration tested, polyploidy was the predominant alteration. These studies indicate that FISH in combination with CYB or BrdU immunfluorescent staining can be sensitive tools for the identification of aneuploidy-inducing agents. (+info)Noscapine is a natural alkaloid compound found in the opium poppy (Papaver somniferum) and some other plants. It has been used medically as a cough suppressant and antitussive agent, acting on the cough center in the brain to reduce the cough reflex. Noscapine is not habit-forming and does not have the same addictive properties as other opium derivatives like morphine or codeine. It also has some anti-inflammatory and mild pain-relieving effects, although it is not typically used for pain management. In addition, noscapine has been studied for its potential anticancer properties, particularly in relation to its ability to inhibit the formation of blood vessels that feed tumors (angiogenesis).
Antitussive agents are medications that are used to suppress cough. They work by numbing the throat and interrupting the cough reflex. Some common antitussives include dextromethorphan, codeine, and hydrocodone. These medications can be found in various over-the-counter and prescription cough and cold products. It is important to use antitussives only as directed, as they can have side effects such as drowsiness, constipation, and slowed breathing. Additionally, it's important to note that long term use of opioid antitussive like codeine and hydrocodone are not recommended due to the risk of addiction and other serious side effects.
"Papaver" is the genus name for the poppy plant family, which includes several species of plants that are known for their showy flowers and often contain medicinal alkaloids. The most well-known member of this family is probably Papaver somniferum, also known as the opium poppy. This particular species contains a number of pharmacologically active compounds, including morphine, codeine, and papaverine, which have been used in various medical contexts for their analgesic, sedative, and vasodilatory effects. However, it's worth noting that the use of Papaver somniferum and its derivatives is tightly regulated due to their potential for abuse and addiction.
Benzylisoquinolines are a type of naturally occurring organic compounds found in various plants. These compounds are derived from the combination of a benzyl group and an isoquinoline ring, hence the name "benzylisoquinolines." They are known to have diverse biological activities, including anti-inflammatory, antispasmodic, and antimicrobial properties. Some well-known examples of benzylisoquinoline alkaloids include papaverine, found in the opium poppy, and berberine, found in various medicinal plants such as goldenseal and barberry. These compounds have been used in traditional medicine for centuries and continue to be studied for their potential therapeutic uses.
Bromine is a chemical element with the symbol "Br" and atomic number 35. It belongs to the halogen group in the periodic table and is a volatile, reddish-brown liquid at room temperature that evaporates easily into a red-brown gas with a strong, chlorine-like odor.
Bromine is not found free in nature, but it is present in many minerals, such as bromite and halite. It is produced industrially through the treatment of brine with chlorine gas. Bromine has a wide range of uses, including as a disinfectant, fumigant, flame retardant, and intermediate in the production of various chemicals.
In medicine, bromine compounds have been used historically as sedatives and anticonvulsants, although their use has declined due to the availability of safer and more effective drugs. Bromine itself is not used medically, but some of its compounds may have therapeutic applications in certain contexts. For example, bromide salts have been used as a mild sedative and anticonvulsant in veterinary medicine. However, their use in humans is limited due to the risk of toxicity.
Noscapine
Levorphanol
Dextrorphan
Charles Derosne
Pentoxyverine
Dimemorfan
Cloperastine
Tipepidine
Promethazine
Pholcodine
Butamirate
Narceine
Racemorphan
Narcotoline
Cold medicine
Opium
Poppy straw
Canadine
Benzylisoquinoline
Latex
TAS2R14
Papaver somniferum
Laudanum
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Papaveretum
Scoulerine
Opiate
Opioid
Isoquinoline alkaloids
Ian A. Graham
Noscapine - Wikipedia
Noscapine - Janusinfo.se
Noscapine | Harvard Catalyst Profiles | Harvard Catalyst
Noscapine hydrochloride | CAS 912-60-7 | Tocris Bioscience
Antitumor Activity of Noscapine in Combination with Doxorubicin in Triple Negative Breast Cancer | PLOS ONE
fMRI Reveals Mitigation of Cerebrovascular Dysfunction by Bradykinin Receptors 1 and 2 Inhibitor Noscapine in a Mouse Model of...
Noscapine.HCl - Lipomed Inc
92621-03-9: Nor-Noscapine - Veeprho
Noscapine Archives - Page 2 of 3 - || MedicScientist :: Total Health Portal || Quality Generic Medicines
Nanomaterials | Free Full-Text | Lipid-Based Nanoparticles: Application and Recent Advances in Cancer Treatment
IRCT | Evaluation and comparison of the effectiveness of three herbal products containing Noscapine (Opiucough, Noscough and...
Preparation and characterization of solid lipid nanoparticles encapsulated noscapine and evaluation of its protective effects...
Sabatino Ventura - Outputs - Monash University
Opportunities to Prevent Overdose Deaths Involving Prescription and Illicit Opioids, 11 States, July 2016-June 2017 | MMWR
Papaver somniferum in seventeenth century (Italy): archaeotoxicological study on brain and bone samples in patients from a...
角田 紀子 (Noriko Tsunoda) - マイポータル - researchmap
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Narcotine3
- Noscapine (also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane) is a benzylisoquinoline alkaloid, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the family Papaveraceae (poppy family). (wikipedia.org)
- Beschreibung Noscapine.HCl Product reference number NOS-285-HC Full chemical name Narcotine.HCl Formula C22H23NO7.HCl Molecular weight 449.89 CAS Number 912-60-7 Supplied as hydrochloride salt Appearance white to off-white cry. (lipomed-shop.com)
- Noscapine (narcotine). (stonecottagegardens.com)
Papaverine1
- Fass environmental information for noscapine from Spasmofen (codeine, methylscopolamine, morphine, noscapine, papaverine) from Meda (downloaded 2019-04-02). (janusinfo.se)
Morphine1
- Extra chemicals such as morphine, noscapine and acetylcodeine were present in the fingerprints of those who had actually taken heroin, due to the way the drug breaks down inside the body. (medicaldevice-network.com)
Hydrochloride4
- Noscapine hydrochloride (Cat. (tocris.com)
- Noscapine hydrochloride is an opioid alkaloid with several actions. (tocris.com)
- Be the first to review Noscapine hydrochloride and earn rewards! (tocris.com)
- Have you used Noscapine hydrochloride? (tocris.com)
Biosynthesis3
- The biosynthesis of noscapine in P. somniferum begins with chorismic acid, which is synthesized via the shikimate pathway from erythrose 4-phosphate and phosphoenolpyruvate. (wikipedia.org)
- Finally, an NAD+-dependent short-chain dehydrogenase (NOS) oxidizes the hemiacetal to a lactone, completing noscapine biosynthesis. (wikipedia.org)
- The enzyme, characterized from the plant Papaver somniferum (opium poppy), participates in the biosynthesis of the isoquinoline alkaloid noscapine. (expasy.org)
Derivatives1
- Noscapine, and its synthetic derivatives called noscapinoids, are known to interact with microtubules and inhibit cancer cell proliferation The lactone ring is unstable and opens in basic media. (wikipedia.org)
Noscough1
- Intervention 1: Intervention group: Patients receive Noscapine Syrup (Noscough®) 20 cc every 6 hours for 5 days. (who.int)
Antitussive2
- Noscapine is often used as an antitussive medication. (wikipedia.org)
- Pretreatment with rimcazole, a σ-specific antagonist, causes a dose-dependent reduction in antitussive activity of noscapine. (wikipedia.org)
Chlorpheniramine1
- Paratusin Obat Untuk Apa - PARATUSIN adalah obat yang mengandung noscapine, chlorpheniramine maleate, glyceryl guaiacolate, paracetamol dan phenylpropanolamine HCl. (missnutrition.info)
Bradykinin1
- Transgenic arcAβ mice, and non-transgenic littermates of 14 months-of-age were either treated with the bradykinin receptors 1 and 2 blocker noscapine or received normal drinking water as control over 3 months ( = 8-11/group) and all mice were assessed using fMRI at the end of the treatment period. (uzh.ch)
Anti-inflammatory1
- Noscapine (NOS) has several anti-inflammatory, anti-angiogenic, and anti-fibrotic effects, but its low solubility and large size results in its lower efficacy in the clinic. (bvsalud.org)
Cough3
- Researchers found that noscapine, which has been used in cough medication for nearly 50 years, reduced tumor growth in mice by 60% and limited the spread of tumors by 65% without causing harmful side effects. (science20.com)
- Since noscapine is approved for use in many countries as a cough suppressant, however, it is available to doctors to prescribe for other uses as well. (science20.com)
- Because noscapine has been used as a cough-suppressant for nearly half a century, it already has an extensive safety record. (science20.com)
Clinical3
- As a natural substance, noscapine cannot be patented, which has limited the potential for clinical trials. (science20.com)
- A synthetic derivative of noscapine has been patented but has not yet reached the clinical testing phase. (science20.com)
- Dr. Barken used noscapine to treat a handful of prostate cancer patients before retiring from clinical practice. (science20.com)
Citation1
- citation needed] Noscapine should not be taken in conjunction with warfarin as the anticoagulant effects of warfarin may be increased. (wikipedia.org)
Receptors1
- Antifibrotic effects of noscapine through activation of prostaglandin E2 receptors and protein kinase A. J Biol Chem. (harvard.edu)
Evaluation1
- Preparation and characterization of solid lipid nanoparticles encapsulated noscapine and evaluation of its protective effects against imiquimod-induced psoriasis-like skin lesions. (bvsalud.org)
Patients1
- In each block, 2 patients will be assigned to noscapine group and 2 patients will be assigned to control group, Blinding description: Patients included to the study are randomized to two groups of drug and control (noscapine syrup and diphenhydramine syrup) by a randomizer (nurse) according to the randomization list taken from www.sealedenvelope.com. (who.int)
Substance1
- Noscapine is a naturally-occurring substance, a non-addictive derivative of opium. (science20.com)
Laboratory1
- No toxic side effects were observed in the laboratory study of noscapine. (science20.com)
Effects3
- Nausea Vomiting Loss of coordination Hallucinations (auditory and visual) Loss of sexual drive Swelling of prostate Loss of appetite Dilated pupils Increased heart rate Shaking and muscle spasms Chest pains Increased alertness Loss of any sleepiness Loss of stereoscopic vision Noscapine can increase the effects of centrally sedating substances such as alcohol and hypnotics. (wikipedia.org)
- Noscapine is effective without the unpleasant side effects associated with other common prostate cancer treatments. (science20.com)
- Noscapine can increase the effects of centrally sedating substances such as alcohol and hypnotics . (cloudfront.net)
Data1
- Risk of environmental impact of noscapine cannot be excluded, since no ecotoxicity data are available. (janusinfo.se)
Treatment4
- Perfusion MRI using an arterial spin labeling technique showed regional hypoperfusion in arcAβ compared to non-transgenic controls, which was alleviated by noscapine treatment. (uzh.ch)
- Similarly, measuring cerebral blood volume changes upon pharmacological stimulation using vessel dilator acetazolamide revealed recovery of regional impairment of cerebral vascular reactivity in arcAβ mice upon noscapine treatment. (uzh.ch)
- Noscapine has previously been studied as a treatment for breast, ovarian, colon, lung and brain cancer and for various lymphomas, chronic lymphocytic leukemia and melanoma. (science20.com)
- Rogosnitzky, director of research at MedInsight Research Institute, points out the significant advantages that noscapine could present as a treatment for prostate cancer. (science20.com)
Found2
- Immunohistological stainings for Aβ deposition (6E10) and related microgliosis (Iba1) in the cortex and hippocampus were found comparable between noscapine-treated and untreated arcAβ mice. (uzh.ch)
- In addition, levels of soluble and insoluble Aβ, Aβ, Aβ were found to be similar in brain tissue homogenates of noscapine-treated and untreated arcAβ mice using electro-chemiluminescent based immunoassay. (uzh.ch)
Publications2
- This graph shows the total number of publications written about "Noscapine" by people in Harvard Catalyst Profiles by year, and whether "Noscapine" was a major or minor topic of these publication. (harvard.edu)
- Below are the most recent publications written about "Noscapine" by people in Profiles. (harvard.edu)
Potential1
- indicates that noscapine has low potential for bioaccumulation. (janusinfo.se)