Abstract:
:1. We studied the stereoselectivity of the effects of the enantiomers of the cardiotonic agent DPI 201-106 (4-[3'-(4"-benzhydryl-1"-piperazinyl)-2'-hydroxypropoxy]-1H-indole-2- carbonitrile, DPI) and its methyl-for-carbonitrile analogue BDF 8784 on cardiac calcium currents (ICa) of guinea-pig ventricular myocytes. The actions of the S- and R-enantiomers were compared with those of the racemate. 2. Racemic, S- and R-DPI depressed ICa in a concentration-dependent manner, the IC50 values were 1.1 mumol l-1 for racemic and S-DPI, and 1.2 mumol l-1 for R-DPI, respectively. Racemic, S- and R-BDF 8784 also reduced ICa, the respective IC50 values were 3.6 mumol l-1 for racemic BDF 8784, 1.3 mumol l-1 for S-BDF 8784 and 1.1 mumol l-1 for R-BDF 8784. 3. Neither the DPI nor the BDF 8784 enantiomers alter the time course of inactivation of ICa. The steady-state inactivation curve for ICa was shifted along the voltage axis to negative membrane potentials. The block of ICa was dependent on the membrane potential and increased with membrane depolarization. 4. Our findings indicate that DPI and BDF 8784 inhibit ICa in a non-stereoselective manner, which contrasts the opposite effects of the DPI enantiomers on Na+ channels.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Ravens U,Pfeifer T,Wettwer E,Grundke Mdoi
10.1111/j.1476-5381.1991.tb12456.xsubject
Has Abstractpub_date
1991-10-01 00:00:00pages
490-4issue
2eissn
0007-1188issn
1476-5381journal_volume
104pub_type
杂志文章abstract::1. The anti-inflammatory effect of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate) on oedema formation, microvascular protein leakage and interstitial fluid pressure (Pif) in rat skin after frostbite injury, was investigated. Alpha-trinositol (40 mg kg body weight(-1)) was administered intravenously as a bolus b...
journal_title:British journal of pharmacology
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abstract:BACKGROUND AND PURPOSE:This paper is intended to assist pharmacologists to make the most of statistical analysis and in avoid common errors. APPROACH:A scenario is presented where an experimenter performed an experiment to test the effects of two drugs on cultured cells. Analysis of the results, expressed as percentag...
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abstract::Following the discovery of the involvement of the ribonucleoprotein TDP-43 in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), a major research focus has been to develop treatments that can prevent or alleviate these disease conditions. One pharmacological approach has been to use TDP-...
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更新日期:2017-12-01 00:00:00
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