Effects of molindone and fluphenazine on the brain concentration of some phenolic and catecholic amines in the mouse and the rat

Br J Pharmacol. 1980 Nov;70(3):475-80. doi: 10.1111/j.1476-5381.1980.tb08726.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Biogenic Amines / metabolism*
  • Brain Chemistry / drug effects*
  • Catecholamines / metabolism*
  • Corpus Striatum / metabolism
  • Fluphenazine / pharmacology*
  • Homovanillic Acid / metabolism
  • Hypothalamus / metabolism
  • Indoles / pharmacology*
  • Male
  • Mice
  • Molindone / pharmacology*
  • Octopamine / metabolism
  • Phenols / metabolism
  • Rats
  • Tyramine / metabolism

Substances

  • Biogenic Amines
  • Catecholamines
  • Indoles
  • Phenols
  • 3,4-Dihydroxyphenylacetic Acid
  • Octopamine
  • Molindone
  • Fluphenazine
  • Homovanillic Acid
  • Tyramine