EFFECTS OF MOLINDONE AND FLUPHENAZINE ON THE BRAIN CONCENTRATION OF SOME PHENOLIC AND CATECHOLIC AMINES IN THE MOUSE AND THE RAT

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Abstract
The concentrations of p‐ and m‐tyramine, dopamine, 3,4‐dihydroxyphenylacetic acid and homovanillic acid were measured in the mouse or rat striatum following the subcutaneous injection of molindone or fluphenazine. The mouse hypothalamic levels of the m‐ or p‐isomers of octopamine were also analysed. Endogenous concentrations of p‐ and m‐tyramine in the mouse striatum and p‐ and m‐octopamine in the mouse hypothalamus were 20.6, 5.7, 9.4 and 1.2ng/g respectively. The rat striatum concentrations of p‐ and m‐tyramine were 12.8 and 3.8 ng/g. The administration of low doses of molindone (1 to 10 mg/kg) produced a reduction in striatal p‐tyramine, an increase in m‐tyramine and an increase in dopamine turnover. Similar effects were produced by all doses of fluphenazine (0.1 to 5 mg/kg) employed. These findings are consistent with those observed after blockade of dopamine postsynaptic receptors. With high doses of molindone (100 mg/kg) the effects on both tyramines and on dopamine metabolism were reversed. These results can be interpreted as molindone acting as a partial agonist. The concentrations of hypothalamic p‐ and m‐octopamine were increased by the higher doses of molindone (20 to 100 mg/kg) employed while lower doses produced no significant effects. All doses of fluphenazine reduced hypothalamic p‐octopamine. These changes seem to depend on differences in the availability of p‐tyramine to be converted into p‐octopamine. These results suggest that molindone acts as a blocker or a partial agonist of dopamine receptor sites and fit well with the proposal of a reciprocal relation between dopamine and tyramine. It is not possible yet to ascertain whether tyramine controls dopamine or vice versa or if it is a direct or a more remote relation.