Maprotiline Alcohol

The hrst step in the preparation of the antidepressant maprotiline (33-5) takes advantage of the acidity of anthrone protons for incorporation of the side chain. Thus treatment of (30-1) with ethyl acrylate and a relatively mild base leads to the Michael adduct saponihcation of the ester group gives the corresponding acid (33-1). The ketone group is then reduced by means of zinc and ammonium hydroxide. Dehydration of the hrst-formed alcohol under acidic conditions leads to the formation of fully aromatic anthracene (33-2). Diels-Alder addition of ethylene under high pressure leads to the addition across the 9,10 positions and the formation of the central 2,2,2-bicyclooctyl moiety (33-3). The hnal steps involve the construction of the typical antidepressant side chain. The acid in (33-3) is thus converted to an acid chloride and that function reacted with methylamine to form the amide (33-4). Reduction to a secondary amine completes the synthesis of (33-5) [33]. 

Lew authors described antidepressant analysis in alternative specimens, such as hair or oral fluid. LC-CID-MS and MS/MS mass spectra libraries for identification of several drugs were employed by Muller et al. [32] for the detection of maprotiline, citalopram, and their desmethyl metabolites in authentic hair specimens extracted ions chromatograms were employed for subsequent antidepressant quantification. Also Klys et al. [33] applied LC-MS/MS to the analysis of blood, urine, and hair specimens in a fatal case due to clomipramine overdose in combination with alcohol. Blood clomipramine and norclomipramine concentrations explained the fatal outcome, and hair analysis confirmed that the deceased was on clomipramine treatment for, at least, 12 months prior to his death. With regard to oral fluid analysis, de Castro et al. [34] developed and validated a... 

Myoclonus due to maprotiline has been reported (13). Further neuromuscular symptoms that have been reported with maprotiline include cerebellar ataxia in a 54-year-old man with a history of unipolar depression and chronic alcohol abuse who was taking maprotiline 200 mg/day (14). The question of whether his history of alcohol abuse contributed by sensitizing his cerebellum to maprotiline-induced ataxia was unresolved. 

In another case, a 49-year-old woman developed cardiogenic shock after taking 60 disulfiram tablets (15 g), 16 clonazepam tablets (8 mg), and six maprotiline tablets (450 mg) in association with alcohol [53 ]. 

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