2, 5-Disubstituted Phthalimides: Design, Synthesis and Anticonvulsant Activity in scPTZ and MES Models.

INTRODUCTION: In this study, fifteen new 2,5-disubstituted analgouges of phthalimide were designed and synthesized using the appropriate synthetic route to evaluate anticonvulsant activity against the Maximal Electroshock (MES) and subcutaneous Pentylenetetrazole (scPTZ) compare to phenytoin as a positive control. The structures of the synthesized compounds were confirmed by FTIR, H-NMR, C-NMR and MASS spectroscopy. METHODS: All the tested compounds were found to be effective in the PTZ model at dose of 60 mg/kg and most of the compounds showed protection against MES test indicative of their ability to inhibit the seizure spread at all dose ranges. Compound 3 illustrated the best efficacy among all compounds and showed more potency than phenytoin in clonic seizure and was potent as phenytoin in tonic seizure. RESULTS & DISCUSSION: Using a model of the Na channel, these derivatives were docked in the active site. Docking studies displayed that all synthesized compounds have more negative binding energy compare to reference drug and inhibition-constant less than phenytoin that means they can block the receptor more efficiently and usually form hydrophobic interactions or hydrogen bond interaction frequently with the domains I, II, III and rarely with domain IV.

Protective effect of magnesium-25 carrying porphyrin-fullerene nanoparticles on degeneration of dorsal root ganglion neurons and motor function in experimental diabetic neuropathy.

Diabetic neuropathy (DN) is the most common peripheral neuropathy and long-term complication of diabetes. In view of the pathological basis for the treatment of DN, it is important to prevent nerve degeneration. Most of the current treatment strategies are symptomatic therapies. In this study, we evaluated the effectiveness of magnesium-25, carrying porphyrin-fullerene nanoparticles, on diabetes-induced neuropathy. Previous studies have suggested that dorsal root ganglion (DRG) neurons comprise a specific target and may be responsible for the known complications of DN. Experimental DN was induced by intraperitoneal injection of streptozotocin (STZ) (45 mg/kg). Different forms of magnesium including (25)Mg-PMC16, (24)Mg-PMC16 and MgCl(2) were administered intravenously in equal dose (0.5 LD(50)) at 48-hr intervals before STZ injection. Peripheral nerves were studied after 2 months of diabetes in groups using qualitative approaches, morphometric analysis of DRG neurons and motor function tests. We showed that STZ-induced DN caused morphological abnormalities in DRG neurons comprising changes in area, diameter and number of A and B cells as well as motor dysfunction in DN. Moreover, our findings indicated that administration of (25)Mg-PMC16 as a magnetic form of Mg improved morphological abnormalities and motor dysfunctions significantly, whereas other forms of Mg were ineffective.