SYMPATHOMIMETIC PROPERTIES OF CHLORPHENTERMINE: METABOLISM, METABOLIC EFFECTS, INTERACTION WITH RESERPINE AND BIOGENIC AMINES

¹ Biochemistry Department, Warner-Lambert Research Institute, Morris Plains, New Jersey

The biochemical properties of chlorphentermine (p-chloro-,-dimethylphenethylamine) as a member of the class of sympathomimetic amines have been examined. Intravenous administration raised free fatty acid levels, but not glucose levels in serum of dogs. Although intravenous doses as high as 36 mg/kg, i.v., did not cause overt CNS stimulation in reserpine-depressed mice, administration of a monoamine oxidase inhibitor in these mice caused chlorphentermine to become clearly excitatory for hours at less than 20 mg/kg. However, determination of norepinephrine levels in tissues (brain, heart, fat, spleen) of several species treated with chlorphentermine, failed to provide clear evidence that CNS, adipose tissue or cardiovascular effects of this compound are mediated by release of the catecholamine. Furthermore, when mice were treated with a dose of reserpine which depleted brain serotonin, but not norepinephrine, their depressed status was not altered by administration of a monoamine oxidase inhibitor plus a second dose of reserpine, which caused an additional release of norepinephrine.

Comparison of rates of metabolism and lipid/aqueous distribution ratios of chlorphentermine and several closely related compounds suggested that the prolonged pharmacological effects of chlorphentermine may be attributable to the influence of the para-chlorine.