CHOLINOLYTICS IN THE TREATMENT OF ANTICHOLINESTERASE POISONING: I. THE EFFECTIVENESS OF CERTAIN CHOLINOLYTICS IN COMBINATION WITH AN OXIME FOR TREATMENT OF SARIN POISONING

1962 ◽  
Vol 40 (1) ◽  
pp. 815-826 ◽  
Author(s):  
I. W. Coleman ◽  
P. E. Little ◽  
R. A. B. Bannard
Keyword(s):  
Atropine Sulphate ◽  
Potent Drug

The protection to sarin poisoning afforded mice by treatment with N-methylpyridinium-2-aldoxime methanesulphonate (P-2-S) in combination with each of 34 cholinolytic compounds used as substitutes for atropine sulphate has been assessed. Twenty-two of the drugs examined in the mouse at a dosage of 50 μmoles/kg gave protection equal to or greater than that afforded by atropine sulphate. The most potent drug was 4′-N-methylpiperidyl 1-phenylcyclopen-tanecarboxylate hydrochloride (G-3063), which was 2.3-fold as effective as atropine sulphate.l-2′-Diethylaminoethyl α-cyclohexyl-α-2″-thienyl glycolate d-bitartrate (Win 5779-6),2′ -diethylaminoethyl 1-phenylcyclopentanecarboxylate hydrochloride (Parpanit), and l-tropyl α-methyltropate hydrochloride were 1.8-, 1.5-, and 1.4-fold as effective, respectively. Eighteen of the compounds were examined in the rat, with 11 showing potency equal to or greater than that shown by atropine sulphate. In this species the most potent drugs were G-3063, which had 4.0 times the activity of atropine sulphate, Win 5779–6 (4.8-fold), and atropine methanesulphonate, followed by 1-cyclohexyl-1-(2′-thienyl)-3-(1″-piperidyl)-propanol-1 hydrochloride (Win 12085) and Parpanit.

CHOLINOLYTICS IN THE TREATMENT OF ANTICHOLINESTERASE POISONING: I. THE EFFECTIVENESS OF CERTAIN CHOLINOLYTICS IN COMBINATION WITH AN OXIME FOR TREATMENT OF SARIN POISONING

1962 ◽  
Vol 40 (6) ◽  
pp. 815-826 ◽  
Author(s):  
I. W. Coleman ◽  
P. E. Little ◽  
R. A. B. Bannard
Keyword(s):  
Atropine Sulphate ◽  
Potent Drug

The protection to sarin poisoning afforded mice by treatment with N-methylpyridinium-2-aldoxime methanesulphonate (P-2-S) in combination with each of 34 cholinolytic compounds used as substitutes for atropine sulphate has been assessed. Twenty-two of the drugs examined in the mouse at a dosage of 50 μmoles/kg gave protection equal to or greater than that afforded by atropine sulphate. The most potent drug was 4′-N-methylpiperidyl 1-phenylcyclopen-tanecarboxylate hydrochloride (G-3063), which was 2.3-fold as effective as atropine sulphate.l-2′-Diethylaminoethyl α-cyclohexyl-α-2″-thienyl glycolate d-bitartrate (Win 5779-6),2′ -diethylaminoethyl 1-phenylcyclopentanecarboxylate hydrochloride (Parpanit), and l-tropyl α-methyltropate hydrochloride were 1.8-, 1.5-, and 1.4-fold as effective, respectively. Eighteen of the compounds were examined in the rat, with 11 showing potency equal to or greater than that shown by atropine sulphate. In this species the most potent drugs were G-3063, which had 4.0 times the activity of atropine sulphate, Win 5779–6 (4.8-fold), and atropine methanesulphonate, followed by 1-cyclohexyl-1-(2′-thienyl)-3-(1″-piperidyl)-propanol-1 hydrochloride (Win 12085) and Parpanit.

A glimpse from the ancient world: What a gold necklace from Tillya-tepe reveals about opium in Afghanistan

Afghanistan ◽  
2020 ◽  
Vol 3 (2) ◽  
pp. 135-173
Author(s):  
Sara Peterson
Keyword(s):  
Opium Poppy ◽  
Ancient World ◽  
Cultural Importance ◽  
Large Seed ◽  
Potent Drug ◽  
Material Evidence ◽  
Societal Role

Among the six excavated burials at Tillya-tepe, in northern Afghanistan, was one occupied by an elite woman wearing a substantial necklace consisting of large gold beads shaped as seed-heads. The scale and fine workmanship of this necklace suggest that it was one of her most important possessions. It can be demonstrated that these large seed-heads are representations of poppy capsules, whose significance lies in the fact that they are the source of the potent drug opium. This necklace is the most outstanding object within a group of items decorated with poppy imagery, all of which were discovered in female burials. The opium poppy has long been a culturally important plant, and the implication of this identification is investigated in several contexts. Firstly, the proliferation of poppy imagery in the female burials at Tillya-tepe is examined, and then there is a discussion of material evidence for opium among relevant peoples along the Eurasian steppes. The particular cultural importance of opium is reviewed, leading finally to a proposal for the societal role of these women.

Designing and Development of Potent Drug Inhibitor to IL13RA2 in Asthma Disease

2011 ◽  
Vol 3 (4) ◽  
pp. 26-29
Author(s):  
Rajath Pujari ◽  
◽  
Basavaraj Udapudi ◽  
Deepak Yaraguppi
Keyword(s):  
Potent Drug

In silico ADME, Bioactivity and Toxicity Parameters Calculation of Some Selected Anti-Tubercular Drugs

2016 ◽  
Vol 6 (6) ◽  
pp. 77 ◽  
Author(s):  
Shashank Shekhar Mishra ◽  
Chandra Shekhar Sharma ◽  
Hemendra Pratap Singh ◽  
Harshda Pandiya ◽  
Neeraj Kumar
Keyword(s):  
Antibiotic Resistance ◽  
In Silico ◽  
Bacillus Calmette Guerin ◽  
Computational Investigation ◽  
Pharmacological Profile ◽  
In Silico Toxicity ◽  
Is Development ◽  
Potent Drug ◽  
Minimal Resistance ◽  
Parameters Calculation

Tuberculosis, one of the most frequent infectious diseases, is caused by a mycobacterium tuberculosis bacteria and it infects several hundred million people each year, results in several million deaths annually. Because there is development of antibiotic resistance, the disease becomes incurable. So, in the absence of effective and potent drug with minimal resistance problems, the mortality rate increases annually. In this computational investigation, we performed In-silico ADME, bioactivity and toxicity parameters calculation of some selected anti-tuberculosis agents. To design a new molecule having good pharmacological profile, this study will provide the lead information.Key Words: Tuberculosis (TB), Bacillus Calmette-Guerin vaccine, TPSA, In Silico toxicity

Exploration of Ion Channels in Mycobacterium tuberculosis: Implication on Drug Discovery and Potent Drug Targets Against Tuberculosis

2020 ◽  
Vol 14 (1) ◽  
pp. 14-29
Author(s):  
Manish Dwivedi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Targets ◽  
Cell Envelope ◽  
Intracellular Pathogen ◽  
Host Immune System ◽  
Transporter Proteins ◽  
Channel Proteins ◽  
Medical Importance ◽  
Potent Drug ◽  
Emergence Of Resistance

Scientific interest in mycobacteria has been sparked by the medical importance of Mycobacterium tuberculosis (Mtb) that is known to cause severe diseases in mammals, i.e. tuberculosis and by properties that distinguish them from other microorganisms which are notoriously difficult to treat. The treatment of their infections is difficult because mycobacteria fortify themselves with a thick impermeable cell envelope. Channel and transporter proteins are among the crucial adaptations of Mycobacterium that facilitate their strength to combat against host immune system and anti-tuberculosis drugs. In previous studies, it was investigated that some of the channel proteins contribute to the overall antibiotic resistance in Mtb. Moreover, in some of the cases, membrane proteins were found responsible for virulence of these pathogens. Given the ability of M. tuberculosis to survive as an intracellular pathogen and its inclination to develop resistance to the prevailing anti-tuberculosis drugs, its treatment requires new approaches and optimization of anti-TB drugs and investigation of new targets are needed for their potential in clinical usage. Therefore, it is imperative to investigate the survival of Mtb. in stressed conditions with different behavior of particular channel/ transporter proteins. Comprehensive understanding of channel proteins and their mechanism will provide us direction to find out preventive measures against the emergence of resistance and reduce the duration of the treatment, eventually leading to plausible eradication of tuberculosis.

Bortezomib blocks Bax degradation in malignant B cells during treatment with TRAIL

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2797-2805 ◽  
Author(s):  
Feng-Ting Liu ◽  
Samir G. Agrawal ◽  
John G. Gribben ◽  
Hongtao Ye ◽  
Ming-Qing Du ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Lines ◽  
Proteasome Inhibitor ◽  
Resistant Cell ◽  
Protein Levels ◽  
Bax Protein ◽  
Degradation Activity ◽  
Potent Drug ◽  
Induced Apoptosis

Proapoptotic Bcl-2 family member Bax is a crucial protein in the induction of apoptosis, and its activation is required for this process. Here we report that Bax is a short-lived protein in malignant B cells and Bax protein levels decreased rapidly when protein synthesis was blocked. Malignant B cells were relatively resistant to tumor necrosis factor–related apoptosis inducing ligand (TRAIL)–induced apoptosis, and this correlated with low basal Bax protein levels. Furthermore, during treatment with TRAIL, the resistant cell lines showed prominent Bax degradation activity. This degradation activity was localized to mitochondrial Bax and could be prevented by truncated Bid, a BH3-only protein; in contrast, cytosolic Bax was relatively stable. The proteasome inhibitor bortezomib is a potent drug in inducing apoptosis in vitro in malignant B-cell lines and primary chronic lymphocytic leukemic (CLL) cells. In CLL cells, bortezomib induced Bax accumulation, translocation to mitochondria, conformational change, and oligomerization. Accumulation and stabilization of Bax protein by bortezomib-sensitized malignant B cells to TRAIL-induced apoptosis. This study reveals that Bax instability confers resistance to TRAIL, which can be reversed by Bax stabilization with a proteasome inhibitor.

scholarly journals PHYTOCHEMICAL EVALUATION OF PUNICA GRANATUM L. LEAF EXTRACT

2017 ◽  
Vol 9 (4) ◽  
pp. 14 ◽  
Author(s):  
P. Sreedevi ◽  
K. Vijayalakshmi ◽  
R. Venkateswari
Keyword(s):  
Metabolic Diseases ◽  
Ethanolic Extract ◽  
Punica Granatum ◽  
Leaf Extracts ◽  
Bioactive Substances ◽  
Pharmaceutical Ingredients ◽  
Wide Range ◽  
Leaf Powder ◽  
Potent Drug ◽  
Punica Granatum L

Objective: This study was conducted to assess the phytochemical constituents in Punica granatum L. Leaf extracts (PGLE) using standard methods.Methods: The leaf powder was extracted using solvents namely aqueous, hydroalcohol, ethanol, ethyl acetate and n-hexane. Qualitative and Quantitative phytochemical screenings of PGLE were assessed by standard methods.Results: All the leaf extracts were positive for a wide range of bio-active compounds except n-hexane. The result has showed that the maximum amount of total phenols (394.16 mg/g DW of extract), total tannins (210.5 mg/g DW of extract), flavanoids (147.4 mg/g DW of extract) and total triterpenoids (112 mg/g DW of extract) were noted in ethanolic extract of P. granatum leaf (EPGL). The biological assay revealed that relevant amount of carbohydrate, protein, lipid and alkaloid in EPGL.Conclusion: The findings of this study concluded that the EPGL had potential bioactive substances that may be used as pharmaceutical ingredients for formulation of new or prospective potent drug to cure wide range of metabolic diseases.

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