A relationship between clomipramine brain concentration and its effect on serotonin metabolism

The relationship between clomipramine (CMP) brain concentration and its inhibitory effect on serotonin (5HT) turnover was investigated in rats treated with a single dose and multiple doses of CMP. CMP reduced the 5-hydroxyindole acetic acid (5HIAA) brain levels in two groups of rats. Concerning the 5HT turnover measured by the probenecid (PBC) technique, there were significant correlations between the CMP brain level (x) and 5HIAA brain level (y) after PBC injections in both acute and chronic experiments. The regression lines for the respective groups were y = 764 - 117 log x (r = 0.84, P less than 0.001) and y = 770 - 97.7 log x (r = 0.68, P less than 0.001). The regression coefficient for the acute experiment was greater than that for the chronic one (p less than 0.001), indicating a less dose-response in the latter. From these findings, the acute dosing with CMP seemed to reduce the 5HT turnover without reference to the dose but a prolonged administration seemed to vary in its effect. This may be due to a compensatory mechanism in the 5HT system induced by chronic CMP-treatment.