Paracetamol is one of the most widely used drug as antipyretic and analgesic for mild to moderate pain. Currently, paracetamol is the first-line choice for pain management and antipyresis. Ion channels are pore-forming proteins that allow the flow of ions across membranes and involved in many cellular processes; drugs acting on ion channels have long been used for the treatment of many diseases. Objective: To estimate the effect of voltage gated ion channel blockers on analgesic activity of Paracetamol and explore the interaction between ion channel blockers and paracetamol on pain behaviour. Materials and Methods: Male albino mice were used. The central antinociceptive activity was determined by hot plate test and formalin test (Phase I; neuropathic pain). Antiinflammatory activity was determined by formalin test (Phase II). Intraperitoneal injection was adopted. Five groups of mice were used. Group 1; control group (1% T80), group 2; treated with (200mg/kg) paracetamol, group 3; treated with different drugs of ion channel blockers, group 4; received standard drugs, Aspirin (200mg/kg) for formalin test (phase II) or tramadol (5mg/kg) for hot plate test and formalin test (phase I), group 5; received combined treatment of ion channel blockers and paracetamol. Results: Pain produced by noxious stimuli (heat and formalin) was significantly reduced by acute administration of paracetamol. Inflammation pain produced by formalin injection was significantly decreased by acute administration of paracetamol. Acute administration of nifedipine showed significant decrease in nociception and inflammation pain. Combined treatment of nifedipine and paracetamol produced antinociceptive and anti-inflammatory activity but less than the additive effect. Verapamil has no analgesic effect in the two models, and did not change the affect of paracetamol analgesic activity when administered together. Phenytoin produces significant decrease in nociceptive pain using hot plate but not in formalin test (Phase I), and produce significant decrease in inflammatory pain (Phase II). The combined treatment of phenytoin and paracetamol showed analgesic activity less than the additive effect. 4-Aminopyridine produces significant antinociceptive and anti-inflammatory activity. The combined administration of 4-aminopyridine and paracetamol showed analgesic activity, which is less than the additive effect using formalin test, while paracetamol analgesic activity is potentiated by 4-aminopyridine using hot plate test. Conclusion: Paracetamol has antinociception and anti-inflammatory activity on pain model used (Hot plate test and Formalin test). Ion channel blockers produce antinociception and anti-inflammatory activity. Verapamil has no effect on nociception or inflammation pain and no effect on paracetamol analgesic activity. Nifedipine, phenytoin and 4-aminopyridine interact with paracetamol producing less additive analgesic effect, except 4-aminopyridine in thermal stimuli (Hot plate) is more sensitive compared to chemical stimuli (formalin test – phase I), where potentiates paracetamol action.
هناء مدحت الزقلعي (2014)

قرحة المعدة والإثناعشر هي من أكثر أمراض الجهاز الهضمي انتشارا وتنتج عن تلف الغشاء المخاطي للمعدة والإثناعشر نتيجة لعدة عوامل أهمها: زيادة إفراز حمض الهيدروكلوريك والعدوى بميكروب الحلائز البوابية والاستخدام المزمن للأدوية المضادة للالتهابات الغيرستيرويدية، إضافة إلى عوامل أخرى مثل التدخين والاستعمال المفرط للكحول. كما تلعب العوامل النفسية والإجهاد العصبي دوراً هاماً في استحداث المرض. أثبتت العديد من الدراسات السابقة على فئران التجارب أن الأدوية المضادة للاكتئاب والتوتر تساعد في تخيف أعراض قرحة المعدة والتي تزيد نسبة الإصابة بها في مرضي الحالات العصبية والنفسية مثل القلق واضطرابات الشخصية والاكتئاب. الهدف من الدراسة: يعتبر الدواء مرتازابين من الأدوية الحديثة لعلاج مرض الاكتئاب، هذا الدواء له آلية تأثير مميزة، عليه صممت هذه الدراسة لدراسة التأثير المضاد للمرتازبين على القرحة المعدية المستحدثة في الفئران البيضاء بواسطة الإيثانول. الخطوات وطرق العلاج: ثم استعمال فئران بيضاء بالغة من الذكور في جميع التجارب. تم إعطاء الإيثانول لكل الفئران عن طريق الفم بجرعة تساوي 1 ملي ليتر/200 جرام من وزن الجسم. ثلاث جرعات مختلفة من عقار المرتازابين (15،30،60 ملجم/كجم) تم إعطاؤها لمجموعات مختلفة من الفئران ساعة قبل تجريعها الإيثانول، وقورنت النتائج بمجموعة مرجعية عولجت بعقار الرانيتيدين 50 ملجم/كجم وهو مثبط لمستقبلات الهيستامين نوع-2. النتائج: بينت نتائج هذه الدراسة أن الجرعات المختلفة لعقار المرتازابين قللت وبشكل فعال من أعداد وأطوال قرحة المعدة الناجمة عن الإيثانول، وكانت الجرعة 30 ملجم/كجم هي الأكثر فعالية في التقليل من حدوث القرحة في الفئران. وأكدت التغيرات الهيستوباثولوجية لنسيج المعدة في المجموعات المختلفة تلك النتائج. إضافة إلى ذلك فإن المعالجة بعقار المرتازابين أدى إلى زيادة طفيفة في حموضة المعدة الكلية، وكانت الزيادة ملحوظة مع استعمال الجرعة العالية من المرتازابين وهي 60 ملجم/كجم. الاستنتاج: نستنج من هذه الدراسة أن المعالجة المسبقة للفئران بالعقار المضاد للاكتئاب المرتازابين قبل استحداث القرحة المعدية بالإيثانول يؤدي إلى التقليل من حدوث هذه القرحة، وهذه الحماية لا ترتبط بالتقليل من إفراز الحمض المعدي والذي كانت زيادته ملحوظة باستخدام الجرعات المختلفة من المرتازابين. Abstract: Despite the availability of many drugs used to treat peptic ulcer disease, the search for new therapy is continued. Antidepressant drugs are among the drugs used since the early 1950s to treat gastric ulcers. In this study the antiulcer activity of 15, 30 and 60 mg/kg of the antidepressant drug mirtazapine has been evaluated on ethanol-induced gastric ulcers in wistar rats. The results have been compared with those of a reference group treated with 50 mg/kg ranitidine and an ulcer control group given distilled water as a pre-treatment before administration of ethanol. All the three doses of mirtazapine have significantly reduced the number (p
هدي يوسف بادي (2015)

ABSTRACT Pumpkin (Cucurbita maxima D.) is an angiosperm belonging to the Cucurbitaceae family generally characterized by climbing herbaceous vine with tendrils. The fruits vary in size, colour, shape and weight and have a moderately hard rind, with a thick edible flesh, and numerous seeds in the fruit which are either plump and tan or soft white.Preliminary phytochemical evaluation on different extracts of seed and fruit of C.maxima reveals the presence of proteins, carbohydrates, flavonoids, saponins, alkaloids, steroids, coumerins, phenolic compounds, terpenoids, and glycosides. A C.maximum contains antioxidants (such as: tocopherols, flavonoids, and phenolic acids, carotenoids or ascorbic acid) which are molecule that are capable of slowing or preventing the oxidation of other molecules. They may protect cells from damage caused by unstable molecules known as free radicals. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions by being oxidized themselves.Free radical scavenging or antioxidant activity of the extract was determined on the basis of their scavenging activity of the stable 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical. Antibacterial activity of the crude extract was determined by Cup-cut agar diffusion method.The pulp and seed extracts showed significant antioxidant activity in a dose-dependent manner with good IC50 values. For the pulp IC50(s) were 4.25 ± 0.05, 3.84 ± 1.18 and 4.12 ± 0.32 for petroleum ether, chloroform and Methanol extracts, respectively. In addition the the seed IC50(s) were 9.22 ± 0.20, 14.5 ± 0.14 and 5.97 ± 1.70 for petroleum ether, chloroform and Methanol extracts, respectively. C.maxima extracts contains antioxidants that prevent the oxidative damage to DNA in presence of DNA damaging agent (Sybr Gold) at a high concentration. The percentage of hydroxyl radical scavenging activity of C. maxima determines the ability of antioxidant to scavenge the hydroxyl radicals. The antioxidant activity of C. maxima extracts has high scavenging activity (thermodynamic property) and relatively high reaction rate (kinetic property); therefore, the second order rate constant (ks) of the H-atom transfer from antioxidant to the hydroxyl radical was seen. The seed extract showed antibacterial properties on both Gram- positive and Gram-negative bacteria used in this study. This means that C. maxima are useful as potential antibacterial agents. It was also observed from this study, the variations in the antibacterial activities of the C. maxima may be due to the differences in their bioactive compositions or concentrations. In conclusion, the physicochemical and preliminary phytochemical evaluation of fruit and seeds of C.maxima provide valuable information regarding their identification, authentication and chemical constituents which may be useful for the standardization and preparation of medicinal plants. The constituents of fruit and seeds of C. maxima may have several medicinal properties and can be utilized for the treatment of various diseases. Further research on this species in Libya may help in the isolation of therapeutically potent compounds which can be finally be subjected to pharmacological activities, thus leading to opening up new avenues in the use of natural products for therapeutic purpose.
إيناس عبدالله السعداوي (2016)