Drugs online research references
Arch Toxicol. 1994;68(6):375-84.
Toxicity of beta-blockers in a rat whole embryo culture: concentration-response relationships and tissue concentrations.
Klug S, Thiel R, Schwabe R, Merker HJ, Neubert D.
Institut fur Toxikologie und Embryopharmakologie, Freie Universitat Berlin, Germany.
Beta-adrenoceptor blockers are widely used drugs for the treatment of cardiovascular diseases. Since beta-blockers cross the placenta, it is essential to consider possible adverse effects on the embryo. Six beta-adrenoceptor blockers were tested at various concentrations (10-5000 microM) in a rat whole embryo culture. Although inducing a very similar pattern of dysmorphogenetic effects (incomplete flexure, disturbed development of the neural tube, the head, the heart and the tail bud), the compounds exhibited a wide range of embryotoxic potency. Estimation of the EC50 (median-concentration producing dysmorphogenesis in 50% of the embryos) for the six compounds revealed differences of more than two orders of magnitude: propranolol 25 microM, alprenolol 30 microM, metoprolol 100 microM, pindolol 150 microM, acebutolol 500 microM, atenolol 4000 microM. Measurements of the concentrations of the various drugs in the cultured embryos at corresponding EC50 levels showed differing values: metoprolol 4.5 microM, propranolol 5.2 microM, alprenolol 8.4 microM, pindolol 9.0 microM, acebutolol 12.5 microM and atenolol 77.0 microM. With regard to the EC50 and the degree of substance transfer to the embryo it can be stated that propranolol and metoprolol show a much higher intrinsic potency to interfere with normal in vitro embryonic development than, e.g. atenolol.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7916561&dopt=Abstract
Can J Physiol Pharmacol. 1994 Apr;72(4):344-52.
Characterization of perfused periaortic brown adipose tissue from the rat.
Matthias A, Richards SM, Dora KA, Clark MG, Colquhoun EQ.
Department of Biochemistry, University of Tasmania, Hobart, Australia.
A technique was developed for the perfusion of periaortic brown adipose tissue (BAT) with a view to assessing vascular system involvement in BAT thermogenesis. The procedure involved cannulation of the thoracic aorta and ligation of the intercostal branches and the distal thoracic aorta. Perfusion was conducted in a buffer-filled chamber using constant flow at 37 degrees C. Lactate dehydrogenase leakage was less than 2%/h, and after 30 min of perfusion the energy charge was 0.72 +/- 0.05 (n = 4) and differed little from freshly sampled interscapular BAT (0.71 +/- 0.03 (n = 7)). Periaortic BAT was indistinguishable from interscapular BAT in enzyme content, mitochondrial size, mitochondrial cristae, lipid content, and cell size. Basal oxygen consumption (VO2) was 64.3 +/- 7.4 mumol.h-1.g-1 wet weight, and basal perfusion pressure was 65 +/- 3 mmHg (1 mmHg = 133.3 Pa). Norepinephrine and isoproterenol each increased VO2 of perfused periaortic BAT in a time-dependent and reversible manner. Half-maximal stimulation of VO2 occurred at 12 nM norepinephrine and 8 nM isoproterenol; maximally stimulated tissue had a VO2 of approximately 150 mumol.h-1.g-1 wet weight. Norepinephrine (50 nM) had no consistent effect on perfusion pressure, but the increase in VO2 by this agonist was completely blocked by 10 microM DL-propranolol and unaffected by phentolamine (1-20 microM) or nitroprusside (0.01-1 mM). Increasing the perfusion flow rate increased pressure and had no effect on basal VO2 but increased the VO2 response due to norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7922865&dopt=Abstract
Circulation. 1994 Oct;90(4):1832-9.
Rate-dependent properties of adenosine-induced negative dromotropism in humans.
Lai WT, Lee CS, Wu SN.
Department of Internal Medicine, Kaohsiung Medical College, Taiwan, Republic of China.
BACKGROUND: The antiarrhythmic effects of sodium channel and calcium channel blockers are known to be rate dependent. Little is known about the rate-dependent effect of adenosine on human atrioventricular (AV) nodal conduction. The purpose of this study was to determine whether the negative dromotropic effect of adenosine is dependent on heart rate. METHODS AND RESULTS: Atrial pacing at 20-millisecond increments decreasing stepwise was performed, and the curves that relate the AH interval to the atrial pacing cycle length were analyzed. The change in AV nodal function was evaluated in three protocols: (1) In 8 group 1A and 6 group 1B patients, an intravenous infusion of adenosine at a dose of 140 and 320 micrograms.kg-1.min-1 was given, respectively; (2) a bolus injection of a fixed dose of adenosine was given to 12 group 2A patients without and 6 group 2B patients with propranolol (0.1 mg/kg) treatment; and (3) in 12 group 3 patients, the AV nodal function was evaluated after intravenous propranolol (0.05 mg/kg) and after subsequent intravenous aminophylline (loading dose, 5 mg/kg; maintenance dose, 0.9 mg.kg-1.h-1). No significant depression of AV nodal function could be demonstrated during intravenous infusion of adenosine. The bolus injection of adenosine could prolong the AH interval, which was dependent on heart rate and more significant at a shorter pacing cycle length. Intravenous propranolol significantly depressed the AV nodal conduction and shifted the curves of the AH interval versus the pacing cycle length to the right. Subsequent intravenous aminophylline shortened the AV nodal conduction time, however, in a rate-independent manner. CONCLUSIONS: The negative dromotropic effects induced by intravenous bolus injection of adenosine became more pronounced at fast atrial pacing rates. These results indicate that adenosine causes rate-dependent prolongation of AV nodal conduction in humans.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7923669&dopt=Abstract
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