Abstract
J.R.Bassett, M.Story and K.D.Cairncross, The influence of orphenadrine upon the actions of a series of sympathomimetic agents, European J. Pharmacol. 4 (1968) 198–204. Orphenadrine potentiated the positive inotropic response to noradrenaline, 3–4 dihydroxynorephedrine, adrenaline and phenylephrine of the isolated atrial preparation of the guinea pig. The responses to metaraminol, synephrine, dopamine, tyramine, ephedrine, amphetamine and isoprenaline were not affected by orphenadrine. The aromatic compounds whose actions were potentiated by orphenadrine all had a hydroxyl group on the beta carbon atom of the side chain and either two phenolic hydroxyl groups or one phenolic hydroxyl group in the meta position In addition, the actions of catecholamines were potentiated to a greater degree than those of the corresponding monophenols. The present results are consistent with the existence of a preferential uptake mechanism for noradrenaine, which can be utilized by certain structurally related amines. Orphenadrine appears to inhibit this preferential uptake mechanism. The failure of orphenadrine to potentiate the actions of isoprenaline, metaraminol and synephrine indicates the importance of substitution on the nitrogen and alpha carbon atom of the alkyi side chain and the position of the phenolic hydroxyl group.
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