Tricyclic antidepressants clinical presentation

Spiker DG, Weiss AN, Chang SS, Ruwitch JF Jr, Biggs JT. Tricyclic antidepressant overdose clinical presentation and plasma levels. Clin Pharmacol Ther 1975 18(5 Part 1) 539 I6. 

Numerous methods have been published for analysis of tricyclic antidepressants. These drugs present various problems to the clinical laboratory (1) the therapeutic serum concentration is 10 to 100 times lower than that of other commonly monitored drugs, and thus to be clinically useful, the method must be able, to measure serum concentrations <50ng/mL (2) these drugs have metabolites that must also be measured and (3) these drugs are structurally similar to common sleep inducers, antihistamines, and many over-the-counter medications used for appetite suppression, which are potential interferences. Of the many hundreds of methods published, only a few have satisfactorily overcome these obstacles. 

III. Clinical presentation. Tricyclic antidepressant poisoning may produce any of three major toxic syndromes anticholinergic effects, cardiovascular effects, and seizures. Depending on the dose and the drug, patients may experience some or... 

Indeed, on the basis of the cyclase assay, amitriptyline is one of the most potent H2-antagonists presently available (KD 0.05 /iM) [ 181, 193]. The dissociation constants for many of the antidepressants are sufficiently low to suggest that the activation of adenylate cyclase by histamine may be inhibited by therapeutically effective concentrations of these compounds [81, 193]. This biochemical action of the tricyclic and tetracyclic antidepressants may thus represent part of the molecular basis of clinical antidepressant activity [193]. It should also be noted that most tricyclic and tetracyclic antidepressants are much more potent inhibitors of H,-receptor responses [67, 120] than they are of the H2-cyclase response, and this property of these compounds may mediate the sedative actions of these drugs [71, 73, 75]. 

A large number of non-tricyclics for which (pharmacological) antidepressant activity is claimed have been described in the last 20 yr, but only those structures are selected whose pharmacology has a pronounced antidepressant profile and/or in which effectiveness in human depression may be expected now or in near future. In general, compounds of which no clinical investigation has been reported more than about 5 yr after their announcement are excluded. In cases of doubt, we made inquiries of the investigators concerned about possibly predicted clinical usefulness. For the presentation of series, the most active or the most pronounced compound of the series is described. 

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