ABSTRACT
Co2MnGa is a Weyl semimetal exhibiting giant anomalous Hall and Nernst effects. Using spin-polarized positron annihilation spectroscopy, we examined a Bridgman-grown Co2MnGa single crystal with a nearly perfectL21-ordered structure and a reference Co2MnAl polycrystal with a Mn-Al-disorderedB2 structure. We found that a large amount of magnetic vacancies (more than 100 ppm) were included in the Co2MnGa crystal but not the Co2MnAl crystal. We discuss possible reasons for the inclusion of vacancies, the role of vacancies in the development of the ordered structure, and the electronic states associated with the vacancies. Toward the development of Co2MnGa-based devices, the manners for reducing vacancies as well as the influence of vacancies on the electrical transport properties should be considered.
ABSTRACT
The effect of cutaneous metabolism on the skin penetration of drugs was analyzed based on a two-layer skin diffusion/metabolism model. In vitro permeation studies of propylparaben and butylparaben with or without an esterase inhibitor, diisopropyl fluorophosphate (DFP), were performed. Pretreatment of the skin with DFP prolonged the lag time for the penetration of intact parabens. Additionally, DFP significantly decreased the total flux of butylparaben, but not that of propylparaben. Model analysis of the penetration profiles revealed that DFP inhibits the cutaneous metabolism without affecting any other processes. To comprehensively understand the relationships among lipophilicity, metabolic rate, and skin permeation of drugs, simulation studies were performed with newly derived equations concerning the permeability coefficient and the lag time for the penetration of both intact and metabolite forms. The analysis revealed that the lag time for the penetration of both intact and metabolite forms becomes shorter with increasing metabolic rate. As the metabolic rate of the drug increases, skin penetration of the intact form decreases whereas that of the metabolite increases. The total flux of intact and metabolite forms increases with increasing metabolic rate, being more obvious for highly lipophilic drugs. This indicates that the permeation of lipophilic compounds such as butylparaben is more highly affected by cutaneous metabolism in the viable layer because these compounds easily penetrate the stratum corneum layer. Consequently, the balance between the permeability of drug across the stratum corneum and the dermis has been implicated to impose a significant influence on the percutaneous absorption of drugs subjected to cutaneous metabolism.
Subject(s)
Parabens/pharmacokinetics , Skin/metabolism , Animals , Diffusion , Male , Models, Biological , Parabens/metabolism , Permeability , Rats , Rats, WistarABSTRACT
To find out selective potassium channel openers (PCOs), we synthesized several 3,5-disubstituted phenylcyanoguanidine derivatives and investigated their structure-activity relationships (SAR). As a result, we discovered selective PCOs having 1,1-diethylpropyl group toward antihypertensive activity.
Subject(s)
Antihypertensive Agents/chemical synthesis , Potassium Channels/drug effects , Animals , Antihypertensive Agents/pharmacology , Cromakalim/pharmacology , Dogs , Intestines/drug effects , Pinacidil/pharmacology , Structure-Activity Relationship , Trachea/drug effects , Trachea/physiology , Urinary Bladder/drug effects , Urinary Bladder/physiologyABSTRACT
Diphenylimidazole and diphenylthiazole derivatives were synthesized and tested as inhibitors of platelet aggregation in in vitro experiments with the rabbit. Diphenylthiazole derivatives (10) were more potent than diphenylimidazole derivatives (4) in inhibiting arachidonic acid-induced platelet aggregation of rabbit platelet-rich plasma. Two diphenylimidazole and eight diphenylthiazole derivatives were evaluated for ex vivo arachidonic acid and collagen-induced platelet aggregation inhibitory activity using guinea pigs. In these compounds, 4,5-bis(4-methoxyphenyl)-2-(1,5-dimethyl-2-pyrrolyl)thiazole (10n) showed strong activity in vitro and ex vivo. The ex vivo activity of 10n was 200 times stronger than that of aspirin. The mechanism of the activity of 10n was the inhibition of cyclo-oxygenase.
