Experimental pharmacological research regarding some newly synthesized benzamides on central nervous system functions

Three newly synthesized benzamides by the Department of Pharmaceutical Chemistry of the Faculty of pharmacy from the University of Medicine and Pharmacy „Carol Davila” Bucharest were tested in order to determine whether these new molecules have similar effects on the central nervous system as those already in therapeutic use belonging to the same chemical group, such as tiapride (neuroleptic) or lidocaine (local anaesthetic). Tests were carried out on NMRI mice which were given new compounds, conventionally named I5C, I14C, and II5C in a dose of 1/20 of the lethal dose 50% (LD50), as previously determined. They received this treatment daily for 21 days. The evasive–investigating capacity of mice was determined using the platform test, and the motor activity using an Activity cage device. The results have shown that compounds I5C and II5C decrease the investigation capacity of the mice; and compound I5C inhibits motor activity, while II5C stimulates it. Thus we concluded that only compounds I5C and II5C have a neuroleptic potential that might be investigated further

Experimental pharmacological research regarding some new quinazolin-4-ones derivatives

A series of new compounds with quinazolin-4-one structure, synthesized by the Pharmaceutical Chemistry Department of the Faculty of Pharmacy of the University of Medicine and Pharmacy “Carol Davila” Bucharest, was studied. Five of them were selected, conventionally named S1, S2, S3, S4, S5, and investigated in terms of their potential influence on the central nervous system (CNS). For this purpose, the antidepressant effect was determined using the forced swimming test; the anxiolytic/ anxiogenic effect was determined using the suspended plus-shaped maze (Ugo Basile); the effect on the motor activity was determined using the Ugo Basile activity cage; and the potential analgesic effect was investigated using the hot plate test (Ugo Basile). Compounds S3 and S5 lowered the motor activity and showed an anxiolytic effect, while S1 and S2 proved to have antidepressant and analgesic effects. A good correlation between antidepressant and analgesic effects was observed, consistent with the fact that analgesic drugs, by increasing norepinephrine and serotonin levels in the pain inhibiting descendent pathways, can be used as co-analgesics in therapy

Development and validation of Triticum phytobiological method as an alternative procedure for investigating in vivo acute toxicity on mice

The goal of this study was to validate an alternative method for determining in vivo acute toxicity using vegetal material instead of laboratory animals, starting from the phytobiological method known also as the Triticum technique. We set out to demonstrate that vegetal cells have similar sensitivity to some toxic agents as animal cells, in which case a statistical correlation could be established. A series of new compounds synthesized by the Romanian National Institute for Chemical Pharmaceutical Research and Development as potential β3 adrenergic receptors agonists were tested for their acute toxicity using classic animal exposure models, before investigating possible anti-diabetic and anti-obesity effects. We then determined whether similar conclusions might be reached exposing vegetal material to the same agents. We successfully demonstrated that plants are affected in a very similar way as animals when exposed to some potentially toxic agents, providing new possibilities for ending unethical animal experiments

New Potential Beta-3 Adrenergic Agonists with Beta- Phenylethylamine Structure, Synthesized for the Treatment of Dyslipidemia and Obesity

Beta-3 adrenergic receptors have important physiological implications, being expressed in many places in the body, including brown adipose tissue. Of the effects studied in preclinical research on lipid metabolism attributable to stimulation of these receptors, we can mention the increased thermogenesis and metabolic rate in the brown adipose tissue, reduction of body weight in obese diabetic rats, lowering of intra-abdominal and subepithelial fat in nonobese and nondiabetic rats, decrease of triglyceride, and increase of HDL cholesterol levels. Carbohydrate metabolism is also changed by beta-3 adrenergic agonists, the most prevalent effects being blood glucose lowering in diabetic rats, increasing insulin secretion of the pancreas, or increasing glucose tolerance. Metabolic effects of 13 newly synthesized compounds of beta-phenylethylamine structure and reference BRL 37344 were investigated in order to identify a potential affinity for beta-3 adrenergic receptors. The antidiabetic and hypolipemiant effects were investigated on a rat model of alloxan-induced diabetes. The results demonstrated that new beta-phenylethylamine derivatives produced marked biological activity over lipid profile. All compounds have markedly decreased the values of total cholesterol, LDL cholesterol, and triglycerides and also have increased the values of antiatherogenic HDL cholesterol. The effects were significantly more intense than the reference substance BRL 37344

Experimental pharmacological research regarding the antidepressant effect of associating doxepin and selegiline in normal mice

The severity and complexity of depression can vary widely among individuals, thus making single drug therapy ineffective in some cases. Taking this fact into account and using a mouse model, we set on investigating the possibility of obtaining a synergism of action between a classical tricyclic antidepressant that inhibits noradrenalin and serotonin reuptake (doxepin), and a modern antidepressant that inhibits type-B monoamine oxidase (selegiline). We measured the antidepressant effect using the forced swimming test and the tail suspension test. We determined motor activity using the Activity Cage test. Our results have shown that the antidepressant effect intensifies significantly in the animals treated with both antidepressants simultaneously compared to those treated only with doxepin. Furthermore, we observed that selegiline decreases the sedative effect of doxepin in the Activity Cage test

DERMATOCOSMETICS FACIAL MASKS FOR TOPICAL TREATMENT OF ACNE

Acne is one of the most common skin diseases affecting mostly adolescents, but can occur also into adulthood. Acne can have profound psychological and social effects, not only for high severity acne, but even in less severe cases. Staphylococcus epidermidis (S. epidermidis) bacteria and Propionibacterium acnes (P. acnes) bacteria are considered to cause this disease. Over time they have used many treatments for acne especially antibiotics, metronidazole showing positive effects and long-lasting. Thus, the purpose of this study was to design and investigate some facial masks in form of membranes with collagen and metronidazole to reduce and prevent adverse effects of conventional treatments using for acne. Type I fibrillar collagen gel was the main component of all masks. Hydrogels based on collagen, metronidazole, starch and polyvinilpyrolidone showed a pseudoplastic behavior with yield stress facilitating their flow and allowing their good manipulation. The membranes were obtained by drying the hydrogels in controlled environment and characterized by water absorbtion and enzymatic degradation. The results relieves that the presence of polymers (starch and polyvinylpirolidone) influence the stability and integrity of the membranes obtain. Based on these results, we could conclude that the obtained masks are potentially usable as a favorable solution in acne disease

Respiratory burst oxidase-D Expression and Biochemical Responses in Festuca arundinacea under Drought Stress

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases catalyze the production of superoxide, a type of reactive oxygen species (ROS). In plants, the NADPH oxidase homologs have been identified as respiratory burst oxidase homologs (Rboh). They are involved in ROS production in response to drought stress. Three entries of tall fescue (Festuca arundinacea Schreb.) were used for analyses in the present study: tolerant (‘Isfahan’) and sensitive (‘Quchan’) accessions to drought during the germination stage, selected from 14 wild populations in Iran, as well as ‘Barvado’ as a control. Partial sequence of the Festuca respiratory burst oxidase-D (FrbohD) gene was isolated from Barvado. We compared expression levels of the FrbohD gene as well as hydrogen peroxide (H2O2), catalase activity and some biochemical responses among the three entries. Gene expression was evaluated for leaf and shoot samples subjected to 3, 6, and 9 d without water. The transcript level of FrbohD, H2O2 content, and catalase activity increased in Quchan under drought stress. It appears that lower levels of FrbohD gene transcription and H2O2 concentration in F. arundinacea leaves contributed to drought stress tolerance in Isfahan. Total protein and total soluble carbohydrate content also increased significantly in Isfahan when it was subjected to drought stress. Isfahan exhibited drought resistance through various strategies, which could serve as selection criteria for improving drought resistance in turfgrass breeding programs

N-Substituted (Hexahydro)-1<i>H</i>-isoindole-1,3(2<i>H</i>)-dione Derivatives: New Insights into Synthesis and Characterization

Novel phthalimide derivatives, namely N-(1,3-dioxoisoindolin-2-yl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide (1a) and N-(1,3-dioxoisoindolin-2-yl)thiophene-2-carboxamide (1b), and hexahydrophthalimide derivative N-(1,3-dioxohexahydro-1H-isoindol-2(3H)-yl)-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide (2), have been synthesized. The phthalimide derivatives were synthesized from phthalic anhydride and 2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide or thiophene-2-carbohydrazide, and the hexahydrophthalimide derivative has been synthesized from hexahydrophthalic anhydride and 2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide. The chemical structures of the compounds are elucidated by Nuclear Magnetic Resonance (NMR) and Infrared (IR) spectra. The new in vitro antioxidant activities of the obtained substances were evaluated using the DPPH method. All tested compounds showed antioxidative activity, the most active compound being 1b. Bioinformatics tools were used for the prediction of pharmacokinetics and pharmacodynamics profiles. Our results showedthat all compounds have a suitable intestinal absorption rate, good BBB and CNS permeabilities and have as molecular targets MAO B, COX-2 and NF-KB, important for antioxidant activities