Vanillin derivatives as antiamnesic agents in scopolamine-induced memory impairment in mice.

Amnesia is a major health problem prevalent in almost every part of the world specifically in old age peoples. Vanillin analogues have played an important role in the field medicines. Some of them have been documented to be promising inhibitors of cholinesterases and could therefore, be used as antidepressant, anti-Alzheimer and as neuroprotective drugs. In this connection, the present study was designed to synthesize new vanillin analogues (SB-1 to SB-6) of varied biological potentials. The synthesized compounds were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and as scavengers of DPPH and ABTS free radicals followed by behavioural antiamnesic evaluation in mice. The compounds; SB-1, SB-3, SB-4 and SB-6 more potently inhibited AChE with IC50 values of 0.078, 0.157, 0.108, and 0.014 µM respectively. The BChE was more potently inhibited by SB-3 with IC50 of 0.057 µM. Moreover, all of the tested compounds exhibited strong antioxidant potentials with promising results of SB-3 against DPPH with IC50 of 0.305 µM, while SB-5 was most active against ABTS with IC50 of 0.190 µM. The in-vivo studies revealed the improvement in memory deficit caused by scopolamine. Y-Maze and new object recognition test showed a considerable decline in cognitive dysfunctions. In Y-Maze test the spontaneous alteration of 69.44 ± 1% and 84.88 ± 1.35% for SB-1 and 68.92 ± 1% and 80.89 ± 1% for SB-3 at both test doses were recorded while during the novel object recognition test the Discrimination Index percentage of SB-1 was more pronounced as compared to standard drug. All compounds were found to be potent inhibitors of AChE, BChE, DPPH, and ABTS in vitro however, SB-1 and SB-3 were comparatively more potent. SB-1 was also more active in reclamation of memory deficit caused by scopolamine. SB-1 and SB-3 may be considered as excellent drug candidates for treating amnesia subjected to toxicological evaluations in other animal models.

Hydrophilically modified self-assembling α-tocopherol derivative as niosomal nanocarrier for improving clarithromycin oral bioavailability.

Synthesis of biocompatible and cost-effective novel nonionic surfactants from renewable resources has been the subject of greater scientific interest for enhancing the bioavailability of less water-soluble drugs. The present study focuses on the synthesis of α-tocopherol-based novel biocompatible nonionic surfactant and its evaluation for forming clarithromycin-loaded niosomal drug delivery system. α-tocopherol was hydrophilically modified through multistep reactions and characterized using mass and 1H NMR spectroscopic techniques. Drug-loaded niosomal vesicles were investigated for entrapment efficiency (%EE), size, polydispersity index (PDI), zeta potential (ζ) and morphology using LC-MS, dynamic light scattering (DLS) and atomic force microscopy (AFM). Blood haemolysis, cell culture and acute toxicity tests were performed to investigate its biocompatibility. In vivo oral bioavailability of clarithromycin loaded in niosomal formulation was studied in rabbits. The vesicles were spherical in shape and entrapped up to 75 ± 2.57% of the drug. They exhibited a homogeneous size distribution with a mean diameter of 245 ± 4.66 nm. The surfactant was quite haemocompatible, low cytotoxic and safe in mice. Improved oral bioavailability of clarithromycin was achieved when carried in α-tocopherol-based niosomes. Results obtained showed that the synthesized amphiphile is biocompatible and has excellent capability for formation of niosomal vesicles and enhancing oral bioavailability of less water-soluble drugs like clarithromycin.

Potential drug-drug interactions in internal medicine wards in hospital setting in Pakistan.

BACKGROUND: Multiple drugs therapies may be the potential source of drug-drug interactions that can result in alteration of therapeutic response and/or increase untoward effects of many drugs. OBJECTIVE: To identify the frequency and levels of potential drug-drug interactions (pDDIs) in internal medicine wards and their association with patients' age, gender, length of hospital stay and number of prescribed medications; and to describe management of frequently identified major or moderate pDDIs. SETTING: Internal medicine wards of two major tertiary care hospitals of Khyber Pakhtunkhwa, Pakistan. METHOD: Micromedex Drug-Reax system was used to screen patient's profiles for pDDIs. Logistic regression was applied to determine the odds ratio for specific risk factors of pDDIs i.e., age, gender, hospital-stay and number of medications. MAIN OUTCOME MEASURE: Overall prevalence and prevalence of contraindicated, major, moderate and minor pDDIs; levels of pDDIs; frequently identified major or moderate interactions; and odds ratios for risk factors. RESULTS: Total, 188 interacting drug-combinations were identified that contributed to 675 pDDIs. Of 400 patients, 52.8% patients were presented with at least one pDDI (overall prevalence), 21.3% with at least one major-pDDI, and 44.3% with at least one moderate-pDDI. Of 675 pDDIs, most were of moderate (63.6%) or major severity (23%); good (61.2%) or fair (25.5%) type of scientific evidence; and delayed onset (50.2%). Most frequently identified major or moderate interactions resulted in 45.3% of all pDDIs. Their potential adverse outcomes included hepatotoxicity, bleeding, ototoxicity, nephrotoxicity, hypoglycemia, hyperglycemia, risk of thrombosis, hypotension, cardiac arrhythmias and reduction in therapeutic-effectiveness. There was significant association of the occurrence of pDDIs with patients' age of 60 years or more (OR = 2.1; 95% CI = 1.3-3.3; p = 0.003), hospital stay of 6 days or longer (OR = 2.6; 95% CI = 1.5-4.5; p = 0.001), and seven or more number of prescribed medications (OR = 5.9; 95% CI = 3.6-9.6; p < 0.001). CONCLUSION: The present study has recorded a high prevalence of pDDIs in internal medicine wards. Patients with old age, longer hospital stay and increased number of prescribed medications were at higher risk.