The effect of clobazam, a 1, 5-benzodiazepine, on kindling seizures was compared with the effects of 1, 4-benzodiazepines, diazepam and bromazepam, in amygdaloid and hippocampal kindled rats. After kindled seizures were established (stage 5 seizure), the test drugs were administered intraperitoneally. In amygdaloid kindled rats, clobazam significantly suppressed the motor seizures (MS) at doses of 20 and 50 mg/kg and significantly shortened the duration of after-discharge (AD) at doses of 10 to 50 mg/kg. Diazepam at doses of 2 to 10 mg/kg and bromazepam at 1 to 5 mg/kg also significantly suppressed the MS and significantly shortened the duration of AD. Similar suppressive effects by these three benzodiazepines were observed in hippocampal kindled rats. From these results, clobazam was found to have a qualitatively similar but weaker anticonvulsive effect than those of 1, 4-benzodiazepines.

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The pharmacokinetic behavior of 4-methylumbelliferone (4-MU), a compound known to be excreted as conjugated metabolites, was studied in mice and the results were compared with those reported in rats. Plasma half-life of the terminal phase (t_{1/2, β}) of mice after an intravenous administration of 4-MU was approximately one-twenty fifth of that of rats. Mice showed a dose dependency in both hepatic and extrahepatic clearances, though dose dependent hepatic clearance is reported to be the main route of elimination in rats. In the same dose range (10-25 mg/kg), the hepatic intrinsic clearance per unit body weight of mice was approximately 5 times larger than that of rats. The blood-to-plasma concentration ratio and the unbound volume of distribution of tissues of mice were smaller than those of rats. It was concluded that the shorter t_{1/2, β} of mice than that of rats may be due to the larger hepatic clearance, the presence of extrahepatic clearance and the smaller volume of distribution.

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The in vitro effect of cinnamic aldehyde, a main component of Cinnamomi Cortex, on platelet aggregation and arachidonic acid (AA) metabolism in human platelets was studied. Cinnamic aldehyde reduced platelet aggregation of both platelet rich plasma and washed platelets, dose-dependently. This compound also decreased the formation of the metabolites of AA such as thromboxane B₂ (TXB₂), 12-hydroxy heptadecatrienoic acid and 12-hydroxyeicosatetraenoic acid in collagen-stimulated washed platelets. The conversion of exogenous [¹⁴C] AA to cyclooxygenase metabolites or 12-lipoxygenase metabolite was not altered significantly by the addition of cinnamic aldehyde. On the other hand, collagen-induced released of [¹⁴C] AA and its metabolites from washed platelets prelabeled with [¹⁴C] AA was markedly reduced by the addition of cinnamic aldehyde. These results suggested that cinnamic aldehyde suppressed the release of AA from platelet membrane phospholipids and then reduced the formation of thromboxane A₂. This inhibitory effect of cinnamic aldehyde on AA release and TXB₂ formation may contribute to reduced platelet aggregation.

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A digoxin radioimmunoassay (RIA) or fluorescence polarization immunoassay (FPIA) kit is frequently used in routine therapeutic drug monitoring (TDM) of β-methyldigoxin (MD) by applying a calibration curve made using the corresponding digoxin calibrators. The variances in the plasma levels (61 samples) and pharmacokinetics (5 patients) due to these two different assay methods for MD were examined in our patients with congestive heart failure. Although the plasma levels of MD measured by these methods were well correlated (r=0.956, p<0.001) to each other over a wide range, RIA showed significantly lower values (p<0.01) in the subtherapeutic range (<0.80 ng/ml), but significantly higher values (p<0.002) in the therapeutic and toxic ranges (0.80-2.00 and 2.00<ng/ml), respectively than FPIA. This trend occurred with increasing concentrations. When MD samples, spiked in normal human plasma, were analyzed by these methods, RIA showed almost true MD values and gave larger values than FPIA with a mean ratio of FPIA to RIA of 0.83. In contrast, normal plasma samples, each spiked with a MD metabolite such as digoxigenin-bisdigitoxide or digoxigenin-monodigitoxide, showed higher values by 10 to 22% in FPIA. These observations are in good agreement with the findings obtained in a pharmacokinetic study that RIA gave significantly higher levels than FPIA, only in the early stage after MD administration, resulting in a smaller total volume of distribution and a larger β value in the elimination phase, as compared with FPIA. These data suggested that the application of FPIA for pharmacokinetic studies of MD should be considered, especially for the calculation of FPIA for pharmacokinetic studies of MD should be considered, especially for the calculation of loading dose and that FPIA may be useful for the routine assay of plasma samples which are collected during the elimination phase in TDM of MD.

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Resident peritoneal cells of monocyte/macrophage lineage were collected by lavage of mice and incubated in vitro for 1-3 d in a culture medium containing various concentrations of macrophage colony-stimulating factor (M-CSF). Stimulation of the cells by zymosan showed that the potency of producing luminol-dependent chemiluminescence had been markedly increased in the CSF-treated cells, indicating increased generation of active oxygen species in these cells. There was an optimal concentration of M-CSF for the enhancement, and the potency of the cells was notably decreased by an overdose of M-CSF. The result was interpreted as being due to the down-regulation of M-CSF receptor.

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Endothelium-dependent vasodilator responses of isolated rat aortic strips precontracted with norepinephrine to acetyl glyceryl ether phosphorylcholine (AGEPC) were compared in the presence and absence of bovine serum albumin (BSA). In the absence of BSA, AGEPC produced endothelium-dependent relaxation at concentrations higher than 10^-6 M, which was considered to be non-specific because similar relaxations were produced by other phospholipids (e.g., lysolecithin) at the same concentration range. This non-specific relaxation was suggested to be caused by changes in membrane fluidity of endothelial cells, since high concentrations of AGEPC and other phospholipids were found to produce structural changes in endothelial cells by phase contrast and electron microscopic studies ; structural changes were never observed after the application of acetylcholine (ACh). In the presence of BSA (2.5 mg/ml), AGEPC caused endothelium-dependent relaxation at concentrations as low as 10^-9M ; however, relaxations by ACh and lysolecithin were not augmented by the presence of BSA. CV-3988 (10^-5M), a specific antagonist of AGEPC, inhibited the relaxations by AGEPC in the presence of BSA. From these results, it is suggested that, in the presence of BSA, AGEPC may produce endothelium-dependent relaxation in a specific manner, which is different from the non-specific relaxations observed in the absence of BSA.

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