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A STAFFORD

Publications and source records attributed to A STAFFORD.

17 recordsLinked to original sources

POTENTIATION OF SOME CATECHOL AMINES BY PHENOXYBENZAMINE, GUANETHIDINE AND COCAINE.

In rabbit isolated atria, cocaine, guanethidine and phenoxybenzamine increased the changes in rate and force of contractions caused by noradrenaline and adrenaline, but did not potentiate isoprenaline. The most likely explanation for this result is that the drugs interfere with one of the mechanisms in the heart by which noradrenaline and adrenaline, but not isoprenaline, are inactivated; a probable mechanism would be the uptake of noradrenaline into storage sites in the tissue. Cocaine, guanethidine and phenoxybenzamine did not potentiate noradrenaline and adrenaline acting on the rabbit isolated duodenum and the rat uterus.

Acetylcholine↗

Adrenaline, anti-adrenaline drugs and potassium movements in rabbits auricles.

Adrenaline (2x10(-6) M) or isoprenaline (7.5x10(-8) M) increased the rate of (42)K uptake and the potassium content of right (spontaneously beating) auricles, but had no effect on potassium movements in quiescent left auricles. Although faster beating induced by electrical stimulation increased the rate of (42)K uptake, the actions of adrenaline were also apparent in auricles which were electrically stimulated so that they beat at a constant rate. The increase in (42)K uptake produced by adrenaline accounted entirely for the increase in potassium content of the tissue. Adrenaline, in concentrations ranging from 2x10(-6) M to 2x10(-4) M, had no effect on (42)K loss from electrically stimulated auricles. The action of adrenaline on (42)K uptake was blocked by dichloroisoprenaline (4x10(-6) M) but not by phenoxybenzamine (1.6x10(-6) M).

Animals↗

Chemical structure and pharmacological activity of some derivatives of digitoxigenin and digoxigenin.

A series of derivatives of digitoxigenin and digoxigenin were prepared and tested for toxicity in the cat and the guinea-pig and on the isolated heart of the 48-hr chick embryo, and for inotropic activity on the cat isolated papillary muscle and the guinea-pig Langendorff heart. The order of relative potency of the compounds remained the same whether they were tested for toxicity or for positive inotropic activity. There are three molecular centres in the cardiac aglycone that are linked closely with cardiac activity. These are: (a) an OH at carbon-3 which can be combined as a glycoside, thus enhancing activity, or esterified or oxidized, producing compounds of lower activity; the maximum intensity of the inotropic response was reduced in the less potent compounds; (b) a 14-beta-OH associated with a cis C-D ring junction, alteration of which abolished activity; (c) an unsaturated cyclobutenolide ring which cannot be reduced without a great decrease in activity.

Animals↗

The duration of action of some cardiac glycosides and aglycones in the guinea-pig.

A method is described for determining the duration of action of cardiac glycosides and aglycones in the guinea-pig. It is based on their property of potentiating the cardiac response to adenosine. The method is particularly suitable for those drugs with a short duration of action, whereas previous methods are more suitable for those drugs with longer durations of action. The duration of action of one-fifth of the lethal dose has been found for: digoxigenin, lanatoside C, ouabain, digitoxigenin-3-one, digitoxin, 3-acetyldigitoxigenin, digoxin, digitoxigenin, lanatoside A; these drugs are arranged in order of increasing duration of action. The possible relationship between the elimination of these drugs and their duration of action can provide an estimate of their rates of elimination.

Biological Transport↗

The uptake of adrenaline and noradrenaline by blood platelets of the pig.

Pig platelets contained 0.2 to 2.6 ng. adrenaline/10(8) platelets (4 experiments). Noradrenaline was not detected in them. When platelet-rich plasma was incubated at 37 degrees with 1 or 10mug. of added catechol amine/ml., the platelets continued to accumulate adrenaline for at least 120 min.; only about one-third as much noradrenaline as adrenaline was taken up. The concentrations of adrenaline taken up by different platelet samples at the end of incubation for 90 min. were proportional to the concentration of adenosine triphosphate in the platelets.

Adenosine Triphosphate↗