femoxetine and 4--alpha-dimethyl-3-tyramine

The ability of desipramine and maprotiline (NA uptake inhibitors), as well as citalopram and femoxetine (5-HT uptake inhibitors) to protect mice against brain NA depletion induced by H 77/77 (4-alpha-dimethyl-m-tyramine), has been compared with their ability to counteract reserpine (2.5 mg kg-1)- or apomorphine (16 mg kg-1)-induced hypothermia and to potentiate TRH (40 mg kg-1)-induced hyperthermia in mice. While both NA uptake inhibitors antagonized the action of H 77/77, maprotiline being weaker than desipramine, femoxetine and citalopram were inactive. However, in contrast to citalopram, femoxetine was active in the other tests, being about twice as weak as maprotiline, which itself was several times weaker than desipramine in those tests. On the basis of the results obtained it is concluded that functional in-vivo tests for NA uptake inhibitors are more sensitive than the H 77/77 biochemical test; moreover, femoxetine, which in-vitro studies is less selective than citalopram, may inhibit the uptake of NA in-vivo.

Topics: Animals; Apomorphine; Body Temperature; Brain; Citalopram; Desipramine; Male; Maprotiline; Mice; Monoamine Oxidase Inhibitors; Norepinephrine; Piperidines; Propylamines; Reserpine; Serotonin Antagonists; Thyrotropin-Releasing Hormone; Tyramine