Neurochemical properties of 3,3-dimethyl-1-[3-(methylamino) propyl]-1-phenylindan HCl (LU 3-049) and selected tricyclic antidepressants.
Lu 3-049 was compared to certain antidepressants on biogenic amine metabolism. Like desipramine, Lu 3-049 was found to possess potent and selective inhibitory effects on norepinephrine uptake. In rat brain and mouse heart, both agents were found to be considerably more potent than imipramine and chlorimipramine. Unlike the latter, Lu 3-049 and desipramine possessed weak inhibitory effects on serotonin uptake in brain or spleen. Brain norepinephrine levels were unaltered following single or repeated doses of either agent. Desipramine caused a marked increase in norepinephrine turnover; Lu 3-049 caused no change or a slight decrease in turnover. Lu 3-049 had neither inhibitory effects on monoamineoxidase activity in brain or liver nor affected norepinephrine release from brain slices. Presumptive of inhibition of amphetamine metabolism, and in decreasing order of potency, iprindole, desipramine and Lu 3-049 elevated brain levels of amphetamine. Thus, Lu 3-049 shares some but not all of the biochemical properties of tricyclic antidepressants.
D000662:Amphetamines / Q000032:analysis; D000818:Animals; D000928:Antidepressive Agents; D001679:Biogenic Amines / Q000032:analysis*; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000378:metabolism; D002997:Clomipramine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism
D000662:Amphetamines; D000928:Antidepressive Agents; D001679:Biogenic Amines; D007189:Indans; D007192:Indenes; D011437:Propylamines; C006174:prindamine; D012701:Serotonin; D008995:Monoamine Oxidase; D002997:Clomipramine; D003891:Desipramine; D009638:Norepinephrine