[Caffeine: traditional and new therapeutic indications and use as a dermatological model drug]. / Koffein: hagyományos és új terápiás indikációk, valamint felhasználás dermatológiai modellvegyületként.

Coffee consumption had already been described in the 15th century. The spreading of coffee drinking was not only a consequence of its delicious aromatic taste, but also of its pharmacological effects, especially due to its caffeine content. In this review, the mechanisms behind its complex stimulatory effects and the latest studies on the possible new therapeutic indications of caffeine are summarized. Several papers reported the neuroprotective (in Alzheimer's and Parkinson's disease) and hepatoprotective profiles of caffeine, and we show the most promising new results about its preventive properties in dermal malignancies. These findings were described both in cell cultures and in vivo. The application of caffeine and coffee in cosmetology and dermatological products is based on their antioxidant property and on the above-mentioned beneficial effects. Caffeine is also presented here as a dermatological model drug due to its hydrophilic profile. It can be used for designing and comparing different novel drug formulations, although beside the transcellular route, the follicular and transappendageal pathways play also important roles in its skin penetration. Taken together, caffeine molecule has many recently discovered beneficial pharmacological effects, but one should be careful with its excessive consumption. It can result in several adverse events if overdosed and in case of regular intake of high doses, after abandonment, withdrawal symptoms may appear. Orv Hetil. 2018; 159(10): 384-390.

Quinidine as an ABCB1 probe for testing drug interactions at the blood-brain barrier: an in vitro in vivo correlation study.

This study provides evidence that quinidine can be used as a probe substrate for ABCB1 in multiple experimental systems both in vitro and in vivo relevant to the blood-brain barrier (BBB). The combination of quinidine and PSC-833 (valspodar) is an effective tool to assess investigational drugs for interactions on ABCB1. Effects of quinidine and substrate-inhibitor interactions were tested in a membrane assay and in monolayer assays. The authors compared quinidine and digoxin as ABCB1 probes in the in vitro assays and found that quinidine was more potent and at least as specific as digoxin in ATPase and monolayer efflux assays employing MDCKII-MDR1 and the rat brain microcapillary endothelial cell system. Brain exposure to quinidine was tested in dual-/triple-probe microdialysis experiments in rats by assessing levels of quinidine in blood and brain. Comparing quinidine levels in dialysate samples from valspodar-treated and control animals, it is evident that systemic/local administration of the inhibitor diminishes the pumping function of ABCB1 at the BBB, resulting in an increased brain penetration of quinidine. In sum, quinidine is a good probe to study ABCB1 function at the BBB. Moreover, quinidine/PSC-833 is an ABCB1-specific substrate/inhibitor combination applicable to many assay systems both in vitro and in vivo.

The AMPA-antagonist talampanel is neuroprotective in rodent models of focal cerebral ischemia.

Cerebroprotection after administration of glutamate receptor antagonists has been well documented. The present study is intended to determine whether the non-competitive alpha-amino-3-hydroxy-methyl-4-isoxazolyl-propionic acid (AMPA) receptor antagonist talampanel, known as antiepileptic drug, has neuroprotective effects in stroke models in rodents. The infarct size was measured in three models of stroke by 2,3,5-triphenyltetrazolium chloride staining. Therapeutic time window was also examined in rats subjected to 1h middle cerebral artery occlusion. The degree of neuroprotection was tested in mice, using 1.5, 2 h or permanent middle cerebral artery occlusions. Effect on photochemically induced thrombosis was investigated in rats applying 30 min time window after brain irradiation. Talampanel reduced the infarct size by 47.3% (p<0.01) after a 30 min delay and 48.5% (p<0.01) after 2 h delay following middle cerebral artery occlusion in rats. In mice, talampanel reduced the extension of the infarcted tissue at the levels of striatum and hippocampus by 44.5% (p<0.05) and 39.3% (p<0.01) after 1.5 h transient ischemia and still caused 37.0% (p<0.05) and 37.0% (p<0.05) inhibitions when 2 h occlusion was applied. In photothrombosis talampanel showed a 40.1% (p<0.05) inhibition. Protective actions of talampanel in various stroke models, in rats and mice, suggest a possible therapeutic role of the compound in stroke patients.