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Some biological effects, both systemic and at the level of adrenals and thyroid, of iodosynephrines and iodothyroadrenalines are studied. lodosynephrines, like synephrine itself but contrary to adrenaline, have no action on L-ascorbic acid and cholesterol level in the adrenals. They do not significantly alter the basal metabolism of normal or thyroidectomized rats. The hyperglycemic activity of diiodo-3:5 synephrine is much less than that of adrenaline, a fact which may explain why iodosynephrines have no action at all on the cardiac rythm or respiratory exchanges. lodothyroadrenalines, having no marked adrenergic activity, show a number of thyromimetic properties: they depress the 131 I thyroidal uptake, counteract to a certain extent the experimental goitre induced by synthetic anti-thyroid agents and display a metamorphogenic activity. They have however no detectable effect on respiratory exchanges or cardiac rythm. Some conclusions are drawn with respect to the relations between activity and structure within the series of sympathomimetic and thyromimetic agents.

Monoiodination, and even more, diiodination, greatly alter the adrenergic properties of synephrine. The tension enhancing activity of iodosynephrines, although lower than that of adrenaline, is higher than that of their iodine-free precursor. They are also characterized by a more prolonged action. They promote important vaso-constriction in the kidney and the perfused isolated leg. A vaso-dilatating effect can be evidenced indirectly, but appears as of little importance and definitively smaller than that of adrenaline and synephrine. Towards the heart, they show, in contradistinction to the positively chronotropic effects of adrenaline and synephrine, a bradycardic action. While monoiodination and especially diiodination of synephrine enhance activities of the α-type but depress those of the, β-type, iodothyroadrenalines exhibit no adrenergic activity. They have no effect on blood pressure, on blood vessels, on the heart, nor on the isolated intestine of the rabbit. Hypotheses are advanced for a tentative explanation of the physiological action of these new substances.

3:5 diiodinated derivatives of several 4 hydroxyphenylalcoylamines were synthetized so as to study some of their adrenergic activities. The compounds were tested on anesthetized and atropinized dogs. The action of the amines and iododerivatives on blood pressure and cardiac rhythm was compared. The data showed that diiodination had not the same effect for each compound. The presence of the secondary hydroxyl on the β- carbon atom was critical. The diiodination of several -4 hydroxyphenylethylamines (tyramine, N methyltyramine, -4 hydroxyamphetamine, N methyl -4 hydroxyamphetamine) was followed by a decrease on the hypertensive response both in intensity and duration. The opposite was observed after iodination of some -4 hydroxyphenylethanolamines (norsynephrine, synephrine, -4 hydroxyephedrine). In this respect the most active product was diiodo -3:5 hydroxyephedrine. On the basis of a comparison between the nuclear magnetic resonance spectra of a few -4 phenolic amines and their diiodo derivatives a hypothesis was developed which explained in part the observed results.

The synthesis and analytical characteristics of four arylethanolamine derivatives are described. They are: monoiodo-3-phenyl-N-methyl-ethanolamine (MIS), diiodo-3:5-phenyl-N-methyl-ethanolamine (DIS), (hydroxy-4'-phenoxy)-4-di-iodo-3:5-phenyl-N-methyl-ethanolamine (TAd2), and (hydroxy-4'-iodo-3'-phenoxy)-4-di-iodo-3:5-phenyl-N-methyl-ethanolamine (TAd3). Iodosynephrines (MIS and DIS) are obtained by direct iodination of synephrine in the presence of ammonia. lodothyroadrenalines (TAd2 and TAd3) are prepared from DIS. After acylation of the amine function of the latter, the resulting product is condensed with pp'-di-anisylionodium bromide. Hydrolysis then yields TAd2, from which TAd3 is obtained by controlled iodination in the presence of ammonia.