The Assessment of Potential Drug Interactions With a New Tricyclic Antidepressant Drug

Abstract

Methods for the investigation of possible interactions with tricyclic antidepressant drugs are described. These methods have been applied to a new compound, Ciba 34276‐Ba, which has been shown to have antidepressant activity. In five normal volunteers tested before and during treatment with Ciba 34276‐Ba, no abnormalities of resting or post‐exercise electrocardiographs occurred. A three‐fold reduction in tyramine‐responsiveness was seen in three normal subjects studied, but no potentiation of the noradrenaline pressor effect occurred. One of six patients given Ciba 34276‐Ba whilst on long‐term treatment with bethanidine showed loss of blood pressure control. The metabolic clearance of antipyrine was unaltered in two subjects studied, showing no evidence of induction or inhibition of hepatic microsomal oxidizing enzymes by Ciba 34276‐Ba.

Mianserin, maprotiline and intracardiac conduction.

“…Previous work has shown different results. Briant & George (1974) noted no effect, Khan (1980) an increase within the normal range and Ghose (1981) a significant increase. Burckhardt-et al (1978) also reported an increase (again reverting to normal by 13 months).…”

“…There have been a number of previous studies of electrocardiographic changes following the administration of both mianserin (Peet et al, 1977;Burgess et al, 1978;Burckhardt et al, 1978;Burrows et al, 1979;Burgess et al, 1979Burgess et al, , 1980Khan, 1980;Kopera, 1980;Wester & Siegers, 1980) and maprotiline (Briant & George, 1974;Khan, 1980;Ghose, 1981). The subjects in some of these studies have been healthy volunteers, in other patients with depression and/or cardiac disease.…”

What are tricyclic antidepressant drugs [letter]?

“…Briant & George (1974) In none of these trials does the comparison seem to have been made in a homogeneous sample of major endogenous depressions. Only such evidence can have relevance to the amine hypothesis of depression which, so far as we know, has never been seriously extended to neurotic reactions with (some) depressive affect.…”

“…In the light of the adequate evidence in favour of an amine hypothesis of depression, Briant & George's (1974) Drs Briant and George reply as follows:…”

“…Our critics, Drs Tait and Todrick, are concerned that in describing Ciba 34276-Ba as a tricyclic antidepressant, we are devaluing the term (Briant & George, 1974). In reply, we would point out that the definition given by the International Union of Pure and Applied Chemists (IUPAC) applies to any chemical structure which possesses three rings.…”