Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To define binding characteristics of drugs, levodopa melanin was prepared with the aid of mushroom tyrosinase. The binding of radiolabeled substances was studied with increasing concentrations of melanin in a fixed volume of potassium phosphate buffer (pH 7.4) at 37 degrees. The affinity and capacity of the drug binding were calculated according to Langmuir's adsorption isotherm. The affinity constant of various sympathomimetic amines such as (-)-amphetamine, (+)-amphetamine, (-)-ephedrine, (+/-)-octopamine, and (+)-norepinephrine ranged from 1.1 to 2.8 X 10(5) M-1. The binding capacity for the amines ranged from 1.4 to 3.2 X 10(-9) mole/mg. Although the capacity of (+/-)-cocaine for binding was similar to that of the amines, the affinity was slightly higher, 8.9 X 10(5) M-1. The binding of atropine to the synthetic melanin appeared to be a saturable process with the affinity and capacity values of 0.2 X 10(5) M-1 and 7.6 X 10(-9) mole/mg, respectively. Although the binding lacks stereoselectivity, the drugs vary in their capacity and affinity to bind with melanin. The observed differential pharmacological and toxicologic properties of drugs in the pigmented tissues may in part be related to their differential bi binding characteristics.
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PMID:Binding characteristics of drugs to synthetic levodopa melanin. 95 12

The myofibrillar calcium sensitivity of mammalian skeletal muscle and cardiac muscle may be increased by myosin light chain kinase (MLCK)-induced myosin phosphorylation5) 13). Here we report increasing calcium responsiveness of frog skeletal muscle fibres (Tibialis anterior, skinned by freeze drying) by MLCK-induced myosin P-light chain phosphorylation and by the non-glycoside, non-sympathomimetic positive inotropic drug pimobendan. Investigation of myosin light chains by two dimensional gel electrophoresis revealed two phosphorylatable P-light chains (LC-2) having the same isoelectric point (5.3 for the unphosphorylated, 5.1 for the phosphorylated form) but different molecular weights (19 and 18 kD, respectively). This pattern of LC-2 is distinct from mammalian skeletal and cardiac muscle (only one phosphorylatable P-light chain in skeletal, two phosphorylatable P-light chains in cardiac muscle with different isoelectric points, but identical molecular weight). The phosphorylation level was about 0.45 mole phosphate/mole P-light chains and could be increased by 16 +/- 3% by the addition of myosin light chain kinase. This procedure increased the isometric tension at pCa 5.5 by 21 +/- 5% while maximum tension (at pCa 4.3) was not affected by MLCK. The new inotropic drug pimobendan (10(-4) M) increased isometric tension at pCa 6 by 48 +/- 4.5%, but maximal tension was not affected. Another positive inotropic drug, sulmazole, has been shown to potentiate the twitch of intact frog Tibialis anterior muscle23) and to increase force of skinned fibres by 21.7 +/- 3.3% at submaximal activation (pCa 6).
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PMID:Myofibrillar calcium sensitivity modulation: influence of light chain phosphorylation and positive inotropic drugs on skinned frog skeletal muscle. 326 85

We have shown previously that histaprodifen and its Nalpha-substituted analogues methylhistaprodifen and dimethylhistaprodifen are highly potent H1-receptor agonists in vivo. The aim of the present study was to examine the influence of four newly synthesized histaprodifen analogues, 3-fluoro-methylhistaprodifen (1), Nalpha-imidazolylethylhistaprodifen (2), bis-histaprodifen (3) and Nalpha-methyl-bis-histaprodifen (4), on the cardiovascular system in the pithed and in the anaesthetized rat. In pithed and vagotomized rats, diastolic blood pressure (which was increased to 80-85 mmHg by vasopressin infusion) was decreased dose dependently by methylhistaprodifen (the reference compound) and by compounds 1-4. The maximum decrease was about 47-50 mmHg for methylhistaprodifen and compounds 1, 2 and 3. Their potencies, expressed as pED50 (the negative logarithm of the dose in mole per kilogram body weight that decreased diastolic blood pressure by 25 mmHg), were 8.31, 8.23, 8.26 and 7.84, respectively. With compound 4 the maximal effect was not achieved at doses up to 1 micromol/kg (the latter dose decreased blood pressure by about 30 mmHg; pED50 approximately 6.5). The vasodepressor effect of the five compounds was attenuated by the H1-receptor antagonist dimetindene (1 micromol/kg) but was not changed by combined administration of the H2- and H3-receptor antagonists ranitidine and thioperamide (1 micromol/kg each), by combined administration of the alpha1- and alpha2-adrenoceptor antagonists prazosin and rauwolscine (1 micromol/kg each) or by the beta-adrenoceptor antagonist propranolol (3 micromol/kg). In anaesthetized rats methylhistaprodifen and compounds 1-4 induced almost the same fall in blood pressure as in pithed and vagotomized animals; the effects were sensitive to blockade by dimetindene (1 micromol/kg). Higher doses of compounds 1 and 2 (1 micromol/kg) increased heart rate in pithed and vagotomized rats in a manner sensitive to propranolol (3 micromol/kg) but insensitive to dimetindene (3 micromol/kg). The same dose of methylhistaprodifen and of compounds 3 and 4 failed to affect heart rate. We conclude that the agonistic potency of compounds 1 and 2 at H1-receptors in the cardiovascular system of the rat equals that of methylhistaprodifen, the most potent histamine H1-receptor agonist available until recently. Compounds 1 and 2 exhibit sympathomimetic activity at high doses.
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PMID:Novel histaprodifen analogues as potent histamine H1-receptor agonists in the pithed and in the anaesthetized rat. 1148 33

In 16 dog heart-lung preparations modified to permit a more accurate measurement of coronary flow, adrenaline or noradrenaline was infused at a rate of 4 mug. base/min. After a 30-min. pause during which the increased oxygen consumption and heart rate, but not the coronary flow, returned to pre-infusion levels, the other sympathomimetic amine was infused for the same length of time. It was found that, mole per mole, noradrenaline is as effective, and probably more so, than adrenaline in raising the oxygen consumption of the heart-lung preparation. The positive chronotropic and coronary dilating action of both amines appear to be equal. It was observed that in any one experiment the second dose of the sympathomimetic amine was slightly more effective than the first dose in raising the oxygen consumption. The level of high-energy phosphorus compounds does not change after adrenaline or noradrenaline administration even at the time when the oxygen consumption rises to as much as 200%. During this period there are no signs of cardiac hypoxia, as can be judged by the good oxygen saturation of coronary venous blood. Single doses of 5 mug. adrenaline or noradrenaline have a consistent positive inotropic effect that lasts about 15 min. when tested on a failing heart. In 12 experiments on non-failing modified heart-lung preparations, a single dose of 5 mug. adrenaline fails to cause a measurable increase in oxygen consumption after 1, 3, 6, or 11 min. in spite of a mild positive chronotropic action. The significance of these findings is discussed and the suggestion made that, when noradrenaline infusions are effective in treating cardiogenic shock in man, part of this effect may be due to its positive inotropic action, thus correcting an element of heart failure that might exist.
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PMID:The effect of adrenaline and noradrenaline on the metabolism and performance of the isolated dog heart. 1369 21