DRUG‐INDUCED CHANGES IN THE FORMATION, STORAGE AND METABOLISM OF TYRAMINE IN THE MOUSE

Abstract

The endogenous concentrations of p ‐ and m ‐tyramine in the mouse striatum were determined by a mass spectrometric integrated ion current technique and concentrations were 21.3 and 6.1 ng/g, respectively. The present results further confirm that the administration of antipsychotic drugs (chlorpromazine, haloperidol, spiroperidol, α‐flupenthixol and (+)‐butaclamol) reduces p ‐tyramine concentrations in the mouse striatum. In contrast, striatal m ‐tyramine showed a tendency to increase, although only in the cases of haloperidol and (+)‐butaclamol were the differences statistically significant. Administration of antipsychotic drugs to mice pretreated with tranylcypromine or clorgyline produced a significant reduction in striatal p ‐tyramine when compared with the concentrations obtained in mice given a monoamine oxidase inhibitor. These results suggest that antipsychotic drugs reduce striatal p ‐tyramine formation. The moderate increases produced by monoamine oxidase inhibitors on striatal m ‐tyramine were not significantly changed after the administration of an antipsychotic. Drugs that reduce dopamine turnover (apomorphine, piribedil, lergotrile, α‐methyl‐ p ‐tyrosine) significantly increased the concentration of striatal p ‐tyramine. No significant changes were observed in striatal m ‐tyramine concentrations after apomorphine, piribedil or lergotrile; α‐methyl‐ p ‐tyrosine produced a reduction in its concentration. Drugs that impair amine storage (reserpine, tetrabenazine, oxypertine) reduced striatal concentrations of p ‐tyramine. The m ‐tyramine concentrations were also reduced by reserpine or tetrabenazine. It is possible that striatal tyramines act as modulators, or transmitters, and control the activity of dopaminergic neurones.