Diamphenethide--a reassessment of its pharmacological action

At a concentration of 1 x 10(-4) M (28.84 micrograms/ml), with a solvent concentration of 1.0% (v/v) ethanol, the deacetylated (amine) metabolite of diamphenethide (DAMD) causes an initial stimulation of activity, followed by suppression, leading to a paralysis within 3 h. These changes are accompanied by an increase in muscle tone of more than 200 mg. However, ethanol alone at a concentration of 1.0% (v/v) causes an initial stimulation of activity and increase in muscle tone (approximately 550 mg). If the concentration of DAMD is kept at 1 x 10(-4) M (28.84 micrograms/ml) but the solvent concentration reduced [e.g., 0.05% (v/v) dimethyl sulphoxide], then only a suppression of motility and flaccid paralysis are observed. This response is also seen at the lower concentration of 10 micrograms/ml, which corresponds to the maximum blood levels of DAMD in vivo. The sodium ionophore monensin induces a suppression of motility, leading to a rapid flaccid paralysis (in approximately 1.5 h at 1 x 10(-7) M, and within a few minutes at higher concentrations). Ouabain, an inhibitor of Na+/K+-ATPase activity, also causes a suppression of motility, but this is accompanied by an increase in muscle tone, leading to a spastic paralysis (in approximately 2.5 h at 1 x 10(-3) M, and 3.5 h at 1 x 10(-4) M). Pretreatment with ouabain (1 x 10(-3) M for 15 min) followed by monensin (1 x 10(-5) M) reverses the original effect of monensin by inducing a rapid spastic paralysis (in approximately 50 min).(ABSTRACT TRUNCATED AT 250 WORDS)