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

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. 1979 British Pharmacological Society