The Effect of Antidepressant Drugs on 24-Hour Rhythms of Tryptophan Metabolism in the Rat

The effect of three antidepressant drugs, imipramine hydrochloride, clomipramine hydrochloride and zimelidine dihydrochloride on plasma free and total TRY concentrations has been examined. The drugs were administered to male Wistar rats in the drinking water at a concentration of 200μgml-1 for up to 15 days. The effects of TRY concentration were complex and, after 2 days, inconsistent. After 14 days, the overall effect of imipramine was to lower free TRY levels and abolish 24-hr variation in free TRY concentration. Zimelidine and clomipramine tended to increase free TRY, particularly at 1300h so that the overall effect was to delay the peak in plasma-free TRY until later in the day. The possible significance of these findings to the mechanism of action of antidepressant drugs in clinical practice is discussed.