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  • General Chemistry  (4)
  • Insulin sensitivity  (3)
  • 1
    ISSN: 1432-1041
    Keywords: Amlodipine ; Hypotension ; Insulin sensitivity ; dihydropyridine ; lipoprotein metabolism ; obese hypertensive patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients. We measured the insulin sensitivity index (SI), determined by the Minimal Model Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients [mean body mass index (BMI) 30.2 kg·m−2] had been on prior treatment with a thiazide diuretic in low dosage and/or a β-adrenoceptor blocker (group A), and 10 matched patients [BMI 31.8 kg·m−2] had been previously untreated (group B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg once daily in 14 patients who were hypertensive after 8 weeks on the lower dosage. At entry (before placebo), SI was slightly but not significantly lower in group A than B [2.7 vs. 3.6×10−4 ml·μU−4·min−1]; fasting plasma insulin was 13.6 vs. 12.9 μU·ml−1. After 6 weeks on placebo, SI averaged 3.7 in group A and 4.4×10−4 μU·ml−1·min−1 in group B; fasting plasma insulin was 14.6 vs. 15.1 μU·ml−1, and glucose 5.5 vs. 5.5 mmol·l−1. After 6 months on amlodipine there were no differences in SI [group A vs. group B, 5.2 vs. 3.8×10−4 ml·μU−1·min−1], fasting insulin [13.0 vs. 12.7 μU·ml−1], glucose [5.4 vs. 5.5 mmol·l−1], serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions. Compared with placebo, amlodipine significantly reduced systolic and diastolic blood pressures. Heart rate, body weight, and 24 h urinary sodium excretion were unaltered. Long-term treatment with amlodipine does not affect insulin sensitivity, circulating insulin or glucose, or lipoprotein metabolism in obese, non-diabetic patients with essential hypertension.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Angiotensin-converting enzyme inhibitor ; Lisinopril ; Hypertension ; Insulin sensitivity ; Lipoprotein metabolism ; physical fitness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract To investigate the effects of antihypertensive treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril on insulin sensitivity and related metabolic variables, the insulin sensitivity index (SI), determined with the Minimal Model Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure were assessed in 24 lean, non-diabetic patients with essential hypertension. Following a double-blind, randomised crossover design, these parameters were measured after a 4-week run-in period, after 8 weeks of lisinopril or placebo, and after an additional 8 weeks on placebo or lisinopril, respectively. Furthermore, the level of physical fitness was estimated using the Conconi bicycle ergometer test. SI was low in this study population (5.6 vs 13.3 · 10−4·min−1·mU−1·1−1 in normal lean control subjects). It did not differ between the placebo run-in phase, the lisinopril phase, and the placebo crossover phase (5.8, 5.5, and 5.4·10−4·min−1·mU−1·1−1, respectively). Moreover, during the administration of lisinopril, no significant changes occurred in fasting plasma insulin and glucose, areas under the glucose and insulin curves, glucose disappearance rate, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions. Heart rate at rest, body weight, and anaerobic threshold remained stable throughout the study. Compliance assessed by pill-counting exceeded 90% at all visits. These findings demonstrate that the ACE inhibitor lisinopril is neutral with regard to insulin sensitivity, plasma insulin and glucose, and lipoprotein metabolism in patients with essential hypertension.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 41 (1991), S. 109-113 
    ISSN: 1432-1041
    Keywords: Amlodipine ; Insulin sensitivity ; serum lipids ; insulin secretion ; healthy volunteers ; blood pressure ; adverse events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (SI). To evaluate the effects of calcium channel blokkade on SI, glucose homoeostasis and lipid profiles, studies were made of SI (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal · day−1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P〈0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol·1−1, respectively) and insulin levels (7.7 vs 7.9 μU·ml−1), SI (10.5 vs 9.6·10−4 × min−1 pro μU·ml−1), serum total Tg, C and lipoprotein C fractions. The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.
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  • 4
    ISSN: 0947-6539
    Keywords: chemoselectivity ; cinchona alkaloids ; clathrates ; osmium tetroxide ; spiro compounds ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Hydrobromination of quinidine (1) with fuming HBr furnished diastereomeric secondary bromides 2a and 2b in 82% yield. After acetylation the resulting bromides 2a-Ac and 2b-Ac could be separated na dconverted stereospecifically into ethylidene rubanes Z)-4 and (E)-4, respectively. cis-Dihydroxylation of (Z)-olefin 4 with OsO4 was shown to be feasible by two catalytic variants, giving the two diastereomeric diols 5a and 5b, separable by chromatography. A simple onepot procedure was developed for converting the sterically hindered 1,2-secondary, tertiary diols stereospecifically into spiroepoxides (5a 6a-Ac; 5b 6b-Ac). Our procedure involves overall inversion of configuration. The procedure complements the Kolb-Sharpless route to epoxides from 1,2-disecondary diols with overall retention of configuration. The other two diastereomeric spiroepoxides 6c and 6d were prepared in one pot under different conditions (chloramine T, then alkali). Two unprecedented tricyclic allylic N,O-acetals (Z)-7 and (E)-7 were also obtained. The structure of spiroepoxide 6c (as a CH2Cl2 monosolvate) and of tricyclic olefinic N,O-acetal (E)-7 was corroborated by X-ray crystallography.
    Additional Material: 1 Ill.
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  • 5
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Chemistry - A European Journal 2 (1996), S. 680-684 
    ISSN: 0947-6539
    Keywords: amino alcohols ; asymmetric syntheses ; dihydroxylations ; diol cleavage Horner-Wittig reaction ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Spiroepoxide 1 was prepared from quinidine and converted into β-amino alcohol 3 (86% over two steps). Dihydroxylation of enantiopure oxazatricylic olefin (E)-4 provided diastereomeric diols 5a and 5b. Stereospecific conversion of 1,2-secondary, tertiary diol 5b into tetracyclic spiroepoxide 6 was accomplished in high yield by a one-pot tosylation-cyclization procedure. 1,2-Diol cleavage with NaIO4 in 80% acetic acid afforded the new tricyclic dehydrorubanone 7, containing the 4-oxa-7-azatricyclo[4.3.1.03,7]-decan-2-one core structure. Similarly, acetylated rubanone 9 was prepared on a 20 g scale. Reduction with NaBH4 in the presence of CeCl3 provided rubanols 10a and 10b (1:1.1). Horner-Wittig reaction of 9 with diethyl cyanomethylphosphonate was (Z)-selective, furnishing unsaturated nitrile (Z)-13. Conversion into the α,β-unsaturated aldehyde (Z)-14 and reduction afforded enartiopure allylic alcohol (Z)-12, which is a new isomer of the key quinidine metabolite 15.
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  • 6
    ISSN: 0044-8249
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0570-0833
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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