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Physiology & Behavior Feb 2017Several studies have investigated the transition of consolidation of recent memory to remote memory in aversively motivated tasks, such as contextual fear conditioning...
Several studies have investigated the transition of consolidation of recent memory to remote memory in aversively motivated tasks, such as contextual fear conditioning (CFC) and inhibitory avoidance (IA). However, the mechanisms that serve the retrieval of remote memories, has not yet been fully understood. Some evidences suggest that the central cholinergic system appears be involved in the modulation of these processes. Therefore, the present study aimed to investigate the effects of a pre-test administration of dicyclomine, a high-affinity M1 muscarinic receptor antagonist, on the retrieval of remote memories in fear conditioning and IA tasks. Male Wistar rats were trained, and after 1 or 28days, the rats received dicyclomine (16 or 32mg/kg, intraperitoneally, i.p.) and were tested in CFC, tone fear conditioning (TFC) and IA tasks. At both time intervals, 32mg/kg dicyclomine induced impairment of CFC. In TFC task only the performance of the rats 28days after training was impaired. The IA task was not affected in any of the studied intervals. These findings suggest a differential contribution of muscarinic receptors on recent and remote memories retrieval revealing a more generalized role in remote memory.
Topics: Acoustic Stimulation; Analysis of Variance; Animals; Avoidance Learning; Conditioning, Classical; Dicyclomine; Dose-Response Relationship, Drug; Fear; Male; Mental Recall; Muscarinic Antagonists; Rats; Rats, Wistar; Receptor, Muscarinic M1; Time Factors
PubMed: 27940145
DOI: 10.1016/j.physbeh.2016.12.008 -
Molecules (Basel, Switzerland) Oct 2018The Emerald Ash Borer (EAB), , Fairmaire, an Asian invasive alien buprestid has devastated tens of millions of ash trees ( spp.) in North America. Foliar phytochemicals...
The Emerald Ash Borer (EAB), , Fairmaire, an Asian invasive alien buprestid has devastated tens of millions of ash trees ( spp.) in North America. Foliar phytochemicals of the genus (Oleaceae): (Green ash), (White ash), (Bush) Bush. (Pumpkin ash), Michx. (Blue ash), Marsh. (Black ash) and . (Manchurian ash) were investigated using HPLC-MS/MS and untargeted metabolomics. HPLC-MS/MS help identified 26 compounds, including phenolics, flavonoids and coumarins in varying amounts. Hydroxycoumarins, esculetin, esculin, fraxetin, fraxin, fraxidin and scopoletin were isolated from blue, black and Manchurian ashes. High-throughput metabolomics revealed 35 metabolites, including terpenes, secoiridoids and lignans. Metabolomic profiling indicated several upregulated putative compounds from Manchurian ash, especially fraxinol, ligstroside, oleuropin, matairesinol, pinoresinol glucoside, 8-hydroxypinoresinol-4-glucoside, verbenalin, hydroxytyrosol-1--glucoside, totarol and ar-artemisene. Further, dicyclomine, aphidicolin, parthenolide, famciclovir, ar-turmerone and myriocin were identified upregulated in blue ash. Principal component analysis demonstrated a clear separation between Manchurian and blue ashes from black, green, white and pumpkin ashes. The presence of defensive compounds upregulated in Manchurian ash, suggests their potential role in providing constitutive resistance to EAB, and reflects its co-evolutionary history with , where they appear to coexist in their native habitats.
Topics: Animals; Chromatography, High Pressure Liquid; Coleoptera; Coumarins; Flavonoids; Fraxinus; Metabolome; Metabolomics; Molecular Structure; Phenols; Tandem Mass Spectrometry
PubMed: 30360500
DOI: 10.3390/molecules23112734 -
The Turkish Journal of Gastroenterology... Mar 2019
Topics: Acute Disease; Dicyclomine; Female; Humans; Middle Aged; Pancreatitis
PubMed: 30459133
DOI: 10.5152/tjg.2018.18411 -
Indian Journal of Pharmacology 2017The study was designed to evaluate possible antihistaminic and anticholinergic activities of . (Comparative Study)
Comparative Study
OBJECTIVE
The study was designed to evaluate possible antihistaminic and anticholinergic activities of .
MATERIALS AND METHODS
Effects of crude ethanolic (Ed.Eth) and effects of crude aqueous (Ed.Aq) extracts of were studied using isolated guinea pig ileum, rabbit jejunum, and rabbit trachea. Tissue responses were recorded using isotonic and isometric transducers, connected with PowerLab data acquisition system.
RESULTS
A dose-dependent (0.1-0.3 mg/ml) rightward shift was demonstrated in histamine concentration-response curves. Whereas a complete relaxation of carbachol (1 μM)-induced contractions in isolated rabbit jejunum (3 mg/ml) and tracheal (10 mg/ml) preparations was observed, similar to dicyclomine at 1 and 3 μM, respectively. However, no significant difference between the effects of Ed.Eth and Ed.Aq was observed.
CONCLUSION
Study provides pharmacological evidence for the presence of antihistaminic and anticholinergic activities in crude extracts of and also highlight its medicinal significance in the management of airway and gastrointestinal disorders.
Topics: Animals; Cholinergic Antagonists; Dicyclomine; Dose-Response Relationship, Drug; Equisetum; Female; Guinea Pigs; Histamine Antagonists; Ileum; Jejunum; Male; Plant Extracts; Rabbits; Trachea
PubMed: 28458431
DOI: 10.4103/0253-7613.201017 -
Frontiers in Pharmacology 2021The genus Thymus is traditionally used for the treatment of hyperactive airways complaints. The purpose of the current study is to investigate the potential tracheal...
The genus Thymus is traditionally used for the treatment of hyperactive airways complaints. The purpose of the current study is to investigate the potential tracheal relaxant effect and possible mechanism(s) of the essential oil of (TS Oil) in isolated guinea pig tracheal tissues. The essential oil was obtained from the fresh erial parts of , and its phyto-components were identified by GC-MS analysis. Guinea pig tracheal preparations were used for testing the tracheal relaxant effect of TS Oil with the determination of the mechanism(s) involved in this relaxation. GC-MS findings reveal that terpenes, fragrance constituents, saponins, and higher fatty acids are present in TS Oil. In isolated guinea pig trachea, TS Oil inhibited carbachol (CCh, 1 µM) and K (80 mM)-induced contractions in a pattern similar to that of dicyclomine. TS Oil, at 0.3 mg/ml, shifted parallel CCh-curves towards the right, followed by a non-parallel shift at higher concentration (1 mg/ml), thus suppressing maximum response in the same manner as produced by dicyclomine. Pretreatment of tissues with TS Oil (1 and 3 mg/ml) also produced a rightward shift of Ca concentration-response curves (CRCs) in the same manner as caused by verapamil. Further, TS Oil at low concentrations (0.3 and 1 mg/ml) shifted isoprenaline-induced inhibitory CRCs towards the left and increased cAMP levels in isolated tracheal homogenates similar to papaverine, a phosphodiesterase (PDE) inhibitor. In the antimicrobial assay performed by the agar well diffusion method, TS Oil was found most active against and where the zone of inhibition measured was 28 mm. Additionally, there was little difference between standard strains of gram-positive and gram-negative bacteria. However, methicillin-resistant (MRSA) showed a small zone of inhibition as compared to standard strains (22 mm). From these results, it can be concluded that the essential oil of has the potential to produce antimicrobial effects while causing tracheal relaxation mediated possibly by anticholinergic effects, Ca channel blockade, and PDE inhibition whereas additional mechanism(s) cannot be ruled out.
PubMed: 33883992
DOI: 10.3389/fphar.2021.615228 -
Saudi Pharmaceutical Journal : SPJ :... Mar 2020, a plant belonging to the family Lamiaceae, is endemic to Ethiopia. In Ethiopian traditional medicine, has been used for the treatment of several respiratory-related...
, a plant belonging to the family Lamiaceae, is endemic to Ethiopia. In Ethiopian traditional medicine, has been used for the treatment of several respiratory-related disorders. The present study was designed to evaluate the bronchodilatory and antimicrobial activities of leaves crude extract (Of.Cr). Ex-vivo experiments were conducted on guinea-pig trachea provided with physiological oxygenated buffer solution using emkaBath setup. The crude extract was analyzed by gas chromatography-mass spectrometry. Of.Cr, showed the presence of terpenes, fragrance components, saponins, and higher fatty acids. Of.Cr when tested on contracted tracheal chains with carbamylcholine (CCh, 1 µM) and high K (80 mM) produced relaxation by showing higher potency against CCh with incomplete inhibition of high K. Dicyclomine, used as a positive control, also showed selectively higher potency to inhibit CCh when compared with its effect against K. In the anticholinergic curves, Of.Cr at 1 mg/mL deflected CCh-induced concentration-response curves (CRCs) competitively to the right like dicyclomine (0.03 µM) and atropine whereas a higher dose of Of.Cr (3 mg/mL) produced a non-parallel shift in the CCh curves like a higher dose of dicyclomine (0.1 µM). In the calcium channel inhibitory assay, Of.Cr at 3 & 5 mg/mL, deflected CRCs of Ca to the right like verapamil, used as positive control. Of.Cr, at concentrations (1-3 mg/mL) increases cAMP levels in isolated tracheal homogenates, similar to positive control phosphodiesterase inhibitor (papaverine). When tested for antibacterial activity against standard and clinical strains, Of.Cr was found more active (MIC 475 µg/ml) against S. aureus (NCTC 6571), while the maximum inhibition (MIC 625 µg/ml) was observed by the extract when tested against MRSA. These results determine the mechanistic pathways of the observed bronchodilatory effect of with a combination of anticholinergic and dual inhibition of phosphodiesterase and voltage-gated Ca channels.
PubMed: 32194329
DOI: 10.1016/j.jsps.2020.01.007 -
Scientific Reports Sep 2019Memory loss is one of the most tragic symptoms of Alzheimer's disease. Our laboratory has recently demonstrated that 'i-Extract' of Ashwagandha (Withania somnifera)...
Memory loss is one of the most tragic symptoms of Alzheimer's disease. Our laboratory has recently demonstrated that 'i-Extract' of Ashwagandha (Withania somnifera) restores memory loss in scopolamine (SC)-induced mice. The prime target of i-Extract is obscure. We hypothesize that i-Extract may primarily target muscarinic subtype acetylcholine receptors that regulate memory processes. The present study elucidates key target(s) of i-Extract via cellular, biochemical, and molecular techniques in a relevant amnesia mouse model and primary hippocampal neuronal cultures. Wild type Swiss albino mice were fed i-Extract, and hippocampal cells from naïve mice were treated with i-Extract, followed by muscarinic antagonist (dicyclomine) and agonist (pilocarpine) treatments. We measured dendritic formation and growth by immunocytochemistry, kallikrein 8 (KLK8) mRNA by reverse transcription polymerase chain reaction (RT-PCR), and levels of KLK8 and microtubule-associated protein 2, c isoform (MAP2c) proteins by western blotting. We performed muscarinic receptor radioligand binding. i-Extract stimulated an increase in dendrite growth markers, KLK8 and MAP2. Scopolamine-mediated reduction was significantly reversed by i-Extract in mouse cerebral cortex and hippocampus. Our study identified muscarinic receptor as a key target of i-Extract, providing mechanistic evidence for its clinical application in neurodegenerative cognitive disorders.
Topics: Animals; Blotting, Western; Dendrites; Dicyclomine; Female; Male; Memory; Mice; Mice, Transgenic; Nerve Regeneration; Neuroprotective Agents; Pilocarpine; Plant Extracts; Receptor, Muscarinic M1; Reverse Transcriptase Polymerase Chain Reaction; Scopolamine; Withania
PubMed: 31570736
DOI: 10.1038/s41598-019-48238-6 -
American Journal of Obstetrics and... Dec 2014Presently, 97.7% of prescriptions for the treatment of nausea and vomiting in pregnancy in the United States are with medications not labeled for use in pregnancy, not...
Presently, 97.7% of prescriptions for the treatment of nausea and vomiting in pregnancy in the United States are with medications not labeled for use in pregnancy, not indicated for nausea and vomiting in pregnancy, and not classified as safe in pregnancy by the Food and Drug Administration. The use of ondansetron for nausea and vomiting in pregnancy has increased from 50,000 monthly prescriptions in 2008 to 110,000 at the end of 2013, despite unresolved issues regarding fetal safety and Food and Drug Administration warnings about serious dysrhythmias. In April 2013, the Food and Drug Administration approved the combination of doxylamine and pyridoxine, specifically for nausea and vomiting in pregnancy symptoms. Now that a safe and effective drug is available in the United States, there is no reason for women to be exposed to a drug of unproven maternal and fetal safety.
Topics: Antiemetics; Dicyclomine; Doxylamine; Drug Approval; Drug Combinations; Female; Heart Defects, Congenital; Humans; Morning Sickness; Ondansetron; Practice Patterns, Physicians'; Pregnancy; Pyridoxine; Serotonin Syndrome; Torsades de Pointes; United States; United States Food and Drug Administration
PubMed: 25151184
DOI: 10.1016/j.ajog.2014.08.017 -
Cancer Management and Research 2016Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%-7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity...
Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%-7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg/d ceritinib dose.
PubMed: 27069372
DOI: 10.2147/CMAR.S96471 -
Saudi Pharmaceutical Journal : SPJ :... Apr 2024Total extract of () expressed potent bronchodilator effect in isolated Guinea pigs' tracheal muscles. Fractionation of total extract ( using liquid-liquid technique...
Total extract of () expressed potent bronchodilator effect in isolated Guinea pigs' tracheal muscles. Fractionation of total extract ( using liquid-liquid technique followed by bronchodilator testing indicated that the activity was trapped to the chloroform (CHCl) soluble fraction. Phytochemical study of the CHCl fraction guided by bronchodilator activity led to the isolation of 7 active flavones of which compounds (Tephroapollin G), (Acetyltephroapollin C), (4''-Dehydroxytephroapollin E), and (Tephroapollin F) were new. Structures were identified using relevant spectroscopic tools including optical rotations and CD data. Compounds , , and lanceolatin A () behaved like papaverine by inhibiting carbachol (CCh) as well as high potassium (K)-mediated contractions at equivalent concentrations with varied potencies whereas (-)-Tephroapollin G () selectively inhibited CCh-mediated contractions but was not found active against high K. -Tephroapollin F () and (-)-Pseudosemiglabrin () in contrast were significantly more potent to abolish CCh induced contraction when compared with high K similar to dicyclomine. Papaverine like dual phosphodiesterase enzyme Ca ion inhibitory activities of and were confirmed indirectly by the bolster of the isoprenaline curves against CCh to the left whereas Ca inhibitory effect of and - was confirmed by the rightward deflection of Ca concentration-response curves (CRCs) towards right with quashing of the maximum response in same fashion like verapamil. Moreover, compounds and at lower concentrations showed selective blockade of muscarinic receptor similar to atropine. Oral administration of the , CHCl and to guinea pigs significantly protected against bronchospasm induced by 0.2 % histamine aerosol .
PubMed: 38435847
DOI: 10.1016/j.jsps.2024.101992