Spectroscopic analysis of charge transfer complex formation and peroxidase inhibition with tricyclic antidepressant drugs: potential anti-thyroid action.
Inspection of the chemical structures of tricyclic antidepressant drugs indicates that they might interfere with the synthesis of thyroid hormones. This iatrogenic potential was demonstrated in vitro by the spectrophotometric detection in both the visible and UV regions of the formation of a complex between antidepressants and iodine. The values of Kc, the formation constant of the drug-iodine complex, were calculated. The concentration of antidepressant which led to a 50% inhibition (IC50) of horseradish peroxidase was also determined. The anti-thyroid activity of drugs can be evaluated from these two parameters, Kc and IC50. The results were compared to those obtained with methimazole, a reference anti-thyroid agent. Antidepressants derived from imipramine appeared to have anti-thyroid activity. This result is now awaiting confirmation in animal experiments.
Rousseau
A
A
Department of Biophysics-Informatique, Faculty of Pharmacy, University of Limoges, France.
Comby
F
F
Buxeraud
J
J
Raby
C
C
D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry*; D013956:Antithyroid Agents / Q000737:chemistry*; D002997:Clomipramine / Q000737:chemistry; D003891:Desipramine / Q000737:chemistry; D006735:Horseradish Peroxidase / Q000037:antagonists & inhibitors*; D007099:Imipramine / Q000737:chemistry; D007455:Iodine / Q000737:chemistry; D007700:Kinetics; D008713:Methimazole / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D000929:Antidepressive Agents, Tricyclic; D013956:Antithyroid Agents; D008713:Methimazole; D007455:Iodine; D006735:Horseradish Peroxidase; D002997:Clomipramine; D007099:Imipramine; D003891:Desipramine