Uptake and disappearance of 4-methyl-alpha-ethylmetatyramine in relation to its releasing action on 5-hydroxytryptamine in the brain.

4-Methyl-alpha-ethylmetatyramine (H75/12) was given intraperitoneally to mice and rats. At various time intervals the animals were killed and the concentration of H75/12 and 5-hydroxytryptamine (5-HT) in the brain and of H75/12 in the heart and, in some cases, in plasma was determined. H75/12 was rapidly taken up by the heart and then disappeared bi- or multiphasically. A maximum concentration of about 6 mug/g was obtained in the brain 30--60 min after the administration of 25 mg/kg. H75/12 disappeared from the brain with a half-life of 1.0 and 1.5 hrs in the mouse and rat, respectively. In the mouse the relative uptake of H75/12 increased with the dose given, i.e. the dose-uptake curve had an upward bending. Significant release of 5-HT in the brain was obtained after a single injection of 25 and 100 mg/kg in the rat and mouse, respectively. The 5-HT release was prevented by tricyclic, antidepressive agents, particularly by chlorimipramine. However, these agents had no certain effect of the uptake of H75/12 in the brain. Moreover, it was not possible to demonstrate a decreased uptake of H75/12 in the rat brain after a chronic, transverse cerebral hemisection, although the monoamine-containing neurones had degenerated as indicated by a complete disappearance of 5-HT. It is concluded that only a minor part of the H75/12 measured is located in monoaminergic neurones. The uptake of H75/12 in the rat brain appeared to be increased in starving animals, possibly indicating decreased metabolism of the drug.