Journal of pharmacological sciences
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Comparative Study
Comparison of four rate-correction algorithms for the ventricular repolarization period in assessing net effects of IKr blockers in dogs.
The utility of corrected and uncorrected QT interval changes for assessing net repolarization delay by I(Kr) (a rapid component of delayed rectifier K(+) currents) blockers was assessed in halothane-anesthetized dogs using the electrocardiogram and monophasic action potential (MAP) recordings with electrical ventricular pacing. Intravenous administration of dl-sotalol (0.2 - 2 mg/kg) prolonged the MAP duration and RR interval, while terfenadine (3 mg/kg) increased the MAP duration but transiently shortened RR interval. ⋯ These results suggest that Matsunaga's and Van de Water's formulae would better predict the net repolarization delay in the in vivo canine model. Also, the risk of drug candidates that may prolong the QT interval should be judged by change in uncorrected QT interval as well as corrected QT interval.
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The most consistent behavioral change caused by olfactory bulbectomy (OBX) is a hyperemotional response to novel environmental stimuli. The aim of this study was to characterize the emotional behavior of OBX mice using the hole-board test. After the olfactory bulbs were lesioned, sham and OBX mice were housed in single cages for 14 days. ⋯ The head-dipping behaviors in single-housed sham and OBX mice were reversed by treatment with diazepam, a typical benzodiazepine anxiolytic. (+/-)-8-Hydroxy-2-(di-n-propylamino) tetraline hydrobromide (8-OH-DPAT), a selective 5-HT(1A)-receptor agonist that has a non-benzodiazepine anxiolytic-like effect, and (+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl benzamide (SNC80), a delta-opioid-receptor agonist, also significantly reversed the number of head-dips in single-housed sham and OBX mice. In conclusion, we suggest that the single-housed OBX mice showed heightened emotional behavior (e.g., increase in head-dipping behavior) in the hole-board test. In addition, we suggest that the hyperemotional behavior characterized by head-dipping behavior in OBX mice was selectively reversed by benzodiazepine and non-benzodiazepine anxiolytics.