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

1 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. 2 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. 3 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. 4 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. 5 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. 6 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.