EFFECTS OF METHOTRIMEPRAZINE, OTHER PHENOTHIAZINES AND RELATED COMPOUNDS ON THE LEVELS OF NOREPINEPHRINE IN THE MOUSE HEART

¹ Department of Chemical Pharmacology, Lederle Laboratories, American Cyanamid Company, Pearl River, New York

The effects of methotrimeprazine, other phenothiazines and related compounds on the levels of radioactivity and norepinephrine in the hearts of mice after pretreatment with H³-norepinephrine have been determined. Administration of methotrimeprazine or normethotrimeprazine at 20 mg/kg i.p. causes a reduction in the radioactivity of the heart after 24 hr, but not after 2.5 hr, and does not prevent the uptake of H³- norepinephrine. Chlorpromazine or imipramine causes an increase in the H³-catechol content after 24 hr and does block the uptake of H3-norepinephrine. Of the phenothiazines and related compounds tested, some had no effect whereas others cause an increase in the radioactivity after 24 hr. Twenty-four hours after methotrimeprazine administration there is a large decline in the H³-catechols with no appreciable change in the endogenous catechol levels. SKF 525A or iproniazid pretreatment interferes with the depleting activity observed. SKF 525A treatment also causes a prolongation of the hypnosis observed after methotrimeprazine administration.