Drug-induced changes in the formation, storage and metabolism of tyramine in the mouse.

1 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.2 The present results further confirm that the administration of antipsychotic drugs (chlorpromazine, haloperidol, spiroperidol, alpha-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.3 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.4 Drugs that reduce dopamine turnover (apomorphine, piribedil, lergotrile, alpha-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; alpha-methyl-p-tyrosine produced a reduction in its concentration.5 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.6 It is possible that striatal tyramines act as modulators, or transmitters, and control the activity of dopaminergic neurones.