Abstract
Dimetacrine (1), 10-[3-(dimethylamino)propyl]-9, 9-dimethyl-acridan, is a tricyclic compound with a central hexagonal ring instead of the heptagonal ring common to most antidepressants. Clinical properties and the value of this drug in the treatment of depressive states, and in a variety of psychic disorders have been well established (2, 3). A previous paper (4) demonstrated the metabolic fate of dimetacrine by means of a radiometric assay.
Recent works (5-8) for the subcellular fractionation of brain tissue permitted the isolation of pinched-off nerve endings or synaptosomes and it has been observed that the bound form of putative central transmitters (9, 10) and the enzymes (11) related to those transmitters, i.e., acetylcholine, serotonin, noradrenaline, cholineacetylase, cholinesterase, 5-hydroxytryptophan decarboxylase and catechol-O-methyltransferase are highly concentrated in the synaptosomal fraction. Compartmentation of certain of these components within synaptosomes has been studied by disrupting the synaptosomes in water or in freezing and thawing procedures, and subsequently separating fractions containing soluble cytoplasmic constituents, synaptic vesicles, synaptic membranes, junctional complexes and intraterminal mitochondria by means of a discontinuous density gradient centrifugation (12-14). These findings suggest that for studying the mode of action of drugs and toxins on the central nervous system, distributions in subcellular organelles of synaptic region must be demonstrated in detail.
The present paper deals with subcellular distribution of H3-dimetacrine in rat cerebral cortex using a discontinuous sucrose density gradient centrifugation and further studies by means of an electron microscope.
