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and toxicity to thyroid follicular cells [30] have all been
proposed as mechanisms for the thyroid dysfunction,
but none of these can explain all of the dierent mani
festations. Data from the current studies suggest one
possibility of how the AMI molecule may in¯uence the
activity of deiodinase in therapy. The same mechanism
of interaction mechanism may also take place at the level
of the thyroid-hormone nuclear receptor. Actually,
whether even the therapeutic eect of AMI is related to
a change of the thyroid hormone function is still an open
question [31].
In summary, our data suggest that in order to mod-
ulate 5¢-T4 deiodination, an AMI analogue must have
(1) an electron-donor group at the 4-position, (2) a
diiodobenzene ring and (3) a lipophilic function at the 1-
position. Thus, it is likely that some degraded products
of AMI could be responsible for the thyrotoxicosis
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Acknowledgements Part of this work was supported by the Hart-
mann Muller Foundation, Study No. 700, University of Zurich,
Switzerland. The authors thank Dr. L. Bigler, Institute of Organic
Chemistry, University Zurich for the LC±MS/MS measurement
and Dr. Marie St-Pierre Dufour, University Hospital Zurich, for
reviewing the manuscript. Part of this work was presented at the
annual meeting of the Federation of American Societies for Ex-
perimental Biology (FASEB) in San Francisco, California in April
1998 and at the 8th International Symposium on Cardiovascular
Pharmacotherapy, Amsterdam, The Netherlands. 28 March ± 1
April 1999.
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a
novel antiarrhythmic