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 homo-vanillic 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 1.2 ng/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.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D005476:Fluphenazine / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008972:Molindone / Q000494:pharmacology*; D009655:Octopamine / Q000378:metabolism; D010636:Phenols / Q000378:metabolism; D051381:Rats; D014439:Tyramine / Q000378:metabolism
D001679:Biogenic Amines; D002395:Catecholamines; D007211:Indoles; D010636:Phenols; D015102:3,4-Dihydroxyphenylacetic Acid; D009655:Octopamine; D008972:Molindone; D005476:Fluphenazine; D006719:Homovanillic Acid; D014439:Tyramine