Thyroid Accumulation and Adverse Effects of Imipramine and Desipramine in Rats after Long-Term Administration

Rousseau, Annick; Marquet, Pierre; Lagorce, Jean F.; Sauvage, Marie; Buxeraud, Jacques; Lachâtre, Gérard; Raby, C

doi:10.1159/000028248

Cited by 8 publications

(1 citation statement)

References 21 publications

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“…17,38 However, plasma concentrations are misleading because thyroidal concentrations of imipramine and desipramine (pharmacologically similar TCAs) were 19 and 6 times, respectively, those found in serum in rats treated with these agents for 4 weeks. 39 Therefore, the thyroid gland concentration of clomipramine in dogs in the current study may have been sufficient to inhibit TPO and result in decreases in T 4 and fT 4 .…”

Section: Discussionmentioning

confidence: 68%

Evaluation of the Effects of Clomipramine on Canine Thyroid Function Tests

Gulikers

Panciera

2003

Veterinary Internal Medicne

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To evaluate the effect of long-term clomipramine administration on the hypothalamic-pituitary-thyroid axis in healthy dogs, 14 healthy adult dogs were enrolled in a prospective study. Clomipramine (3 mg/kg PO q12h) was administered to all dogs beginning on day 0, and continued for 112 days. Serum total thyroxine (T4), free thyroxine (fT4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3; rT3), and thyroid-stimulating hormone (TSH) were measured on days 0, 7, 28, 42, 56, and 112. Thyrotropin-releasing hormone (TRH) response tests were performed concurrently. Significant decreases were noted in serum T4, f4, and rT3 concentrations beginning on day 28 through the end of the study period. The lowest mean (+/-SEM) concentrations of T4 (26 +/- 1.2 to 17 +/- 0.5 nmol/L) and rT3 (1.21 +/- 0.13 to 0.83 +/- 0.08 nmol/L) occurred at day 112, whereas the lowest mean fT4 (29 +/- 2.4 to 18 +/- 1.7 pmol/L) was found on day 56 of clomipramine treatment. The effect of treatment over time on serum T3 concentration also was significant, but the deviation in T3 from baseline was variable. No significant effect of clomipramine treatment was noted on either pre- or post-TRH TSH concentrations. The 35 and 38% decreases in serum T4 and fT4 concentrations, respectively, during clomipramine administration may lead to a misdiagnosis of hypothyroidism. Although no evidence of hypothyroidism was noted in this study population, subclinical hypothyroidism may have occurred. A longer duration of treatment might further suppress thyroid function, and concurrent illness or other drug administration might exacerbate clomipramine's effects.

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Section: Discussionmentioning

confidence: 68%

Evaluation of the Effects of Clomipramine on Canine Thyroid Function Tests

Gulikers

Panciera

2003

Veterinary Internal Medicne

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Electrochemical Oxidation of Desipramine Drug in the Presence of 4,6‐Dimethylpyrimidine‐2‐thiol Nucleophile in Aqueous Acidic Medium

2015

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1IntroductionTr icyclic antidepressant drugs (TCAs)s uch desipramine (3-(10,11-Dihydro-5H-dibenzo[b,f]azepin-5-yl)-Nmethylpropan-1-amine), are active ingredients of psychiatric drugs widely used in the treatment of depressive disorders [1].T hese tricyclic antidepressants (TCAs)a re used primarily in the clinicalt reatment of mood disorders such as major depressive disorder, dysthymia, and bipolar disorder, especially of the treatment-resistant variants.H owever,t heir overdosei sf atal to the centraln ervous system and may result in drowsiness,c onvulsions,r espiratory disorders,o phthalmoplegia and finally coma [2].M oreover, this drug has also proved to be effective for the treatment of otheri llnesses in addition to depression [3].D esipramine is ad ibenzazepine compound belongs to an important family of antidepressant drugs that inhibits the reuptake of norepinephrine.D esipramine is an active metabolite of imipramine,h avingw ide applicability in pharmacological fields as antinociceptive [4] antithyroid [5],f or detection blood in urine [ 6],i ndeed all these activities are increased upon complexation with electron acceptors.In recent years considerable effort has been expended in elucidating the mechanisms of electrolytic oxidation of heterocyclic nitrogen and amine compounds as well as other nitrogen containing species.O ne of the prominent characteristics of amines is oxidativec oupling to form av ariety of dimerized derivatives of the original parent compounds [7].C ertain heterocyclic nitrogen compounds such as dibenzazepines which may be considered as being derivedf rom desipraminea lso undergo as imilar coupling processo no xidation [8][9][10].E lectrooxidation of compounds containing amineg roups were reported by many workers at different conditionss ucha sa queous and non aqueouss olvents or at various pH values [7].A mong the electrochemical methods,c yclic voltammetry presents very versatile tool fort he kinetic and mechanistic studies of electron transferr eactions and electrochemicals ynthesis of organic and inorganic compounds.F urthermore, cyclic voltammetry is knowna sapowerfult echnique for the investigation of electrochemicalr eactions that are coupled with chemicalr eactions [11][12][13][14][15][16].Thee lectrochemical behavioro ft he desipramine was consistentw ith an ECE mechanism [17].C onsidering these facts,t he aim of this work is to study the electrochemical oxidation behavioro fd esipramine in the presenceo fD MPT at ag lassy carbone lectrode using cyclic voltammetry and controlled-potential electrolysis methods in an aqueous acidic medium. This work also represents an electrochemical process for the synthesis of anew derivative of dibenzazepine via electrochemical oxidation of desipramine( 1) in the presenceo fD MPT under green conditions.Abstract:E lectrochemical oxidation of desipramine (DES) has been studied in the presence of 4,6-dimethylpyrimidine-2-thiol (DMPT) as nucleophile in acidic mediumb ym eans of cyclic voltammetry,c ontrolled-potential electrolysis and spectroscopi...

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