I. COMPARISONS OF EFFECTIVENESS IN DECREASING EPINEPHRINE TOXICITY IN MICE
Abstract
The ability of chemical compounds to exert adrenergic blocking (sympatholytic) activity was usually detectable following oral administration of the compounds to mice since they became resistant to the lethal effects of epinephrine injected intraperitoneally. Reduction of epinephrine toxicity in mice was demonstrated with adrenergic blocking drugs such as yohimbine and Priscol, but not with the dioxane derivative, 933 F, although the closely related compound, 883 F, proved effective following subcutaneous administration. Effectiveness was demonstrated with Dibenamine (N,N-dibenzyl-β-chloroethylamine). The most effective compounds were representatives of three chemical series of new β-chloroethylamines including the hydrochlorides of N-benzohydryl-N-ethyl-β-chloroethylamine, N-ethyl-N-(1-naphthylmethyl)-β-chloroethylamine and N-[β-(2-biphenylyloxy)-ethyl]-N-ethyl-β-chloroethylamine. These compounds also induced "epinephrine reversal" in cats and dogs and in the latter animal they diminished, blocked or reversed the pressor responses which follow increased sympathetic nervous activity induced by a variety of means.
The reduction of epinephrine toxicity in mice with a given compound does not necessarily indicate adrenergic blocking activity since the parasympatho-mimetic drug, Mecholyl, also reduced epinephrine toxicity.
Footnotes
- Received April 14, 1948.
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