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  • 1
    ISSN: 1432-1912
    Keywords: Skeletal muscle ; Chloride channel conductance ; Taurine binding site ; Taurine analogues ; Structure-activity relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rat skeletal muscle, taurine was proposed to interact with a low affinity binding site on sarcolemmal phospholipids near chloride channel, increasing chloride conductance (GCI). In an attempt to evaluate the structure-activity relationship between taurine and its binding site, a series of N-azacycloalkenyl analogues of taurine (A: N-(1′aza-cyclopenten-2′yl)-2-aminoethane sulfonic acid; B: N-(1′-aza-cyclopenten-2′-yl)-2-aminoethane sulfonic acid; C: N-(1′aza-cyclopenten-2′-yl)-3-amino-propane sulfonic acid; D: N-(1′aza-cyclopenten-2′-yl)-3-aminopropane sulfonic acid) have been synthetized and tested in vitro on rat extensor digitorum longus (EDL) muscle. In spite of the presence of a bulky and lipophilic 5 or 7 membered heterocycle linked to the taurine amino group, analogues A and B determined an increase of GCI, although less potently than taurine. Also 3-aminopropane sulfonic acid (homotaurine), tested in comparison, showed less activity in increasing GCI with respect to taurine, probably for the increased distance between charged groups. Taurine analogues C and D, which differ from compounds A and B for an additional methylene group, showed much lower activity in increasing GCI. It has been reported that guanidinoethane sulfonate (GES) displaces taurine from the low affinity site on sarcolemma by only 7%. This compound, characterized by lower charge density on the guanidinium cationic head, applied in vitro on EDL muscle, show reduced taurine-like activity in increasing GCl. Our results support the hypothesis that the effect of taurine on muscle GCI is due to a specific binding on a low affinity site on sarcolemma and that charge delocalization reduces the binding probability more than the substitution of the primary amino group or the increased distance between charged groups.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: metoprolol ; chlorthalidone ; essential hypertension ; treatment schedule ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a multicentre, double-blind (DB), within-patient study, the antihypertensive effectiveness and tolerability of two oral administration schedules of metoprolol (M) 100 mg b.i.d. versus 200 mg once daily (o.d.), were investigated in 103 outpatients with mild to moderate essential hypertension. The study lasted 14 weeks and was divided into 3 periods: a) 2 weeks of single-blind (SB) placebo wash-out; b) 4 weeks of SB administration of M 100 mg b.i.d.; at the end of the second week of this period, chlorthalidone (C) 25 mg was added in patients with a recumbent diastolic blood pressure (BP) still 〉95 mmHg and was continued throughout the following period; and c) DB cross-over administration of M 200 mg/d for 4 weeks on a b.i.d. schedule and 4 weeks on a once daily schedule. In comparison with pretreatment values, heart rate and systolic and diastolic BP were reduced (p〈0.001) by both M administration schedules; there was no differences between the once and twice daily treatment regimens. During M once daily, betablockade was still maintained over 24 hours or longer, as the heart rate remained significantly lower than the basal value. In 57 patients, C was added at the end of the second week of SB M administration, and a further decrease in BP was observed; again, there was no significant change during once and twice daily M administration. Unwanted effects during M treatment were of minor severity, and the majority occurred when C, too, was added.
    Type of Medium: Electronic Resource
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