MECHANISM OF ACTION OF ACCELERANTS

Summary.— Liquids such as dimethyl sulphoxide (DMSO), n-decylamine or di-2-ethylhexylamine, which are able to accelerate the penetration through the skin of drugs dissolved in them, also cause varying degrees of inflammation and increased capillary permeability. The present work was undertaken to see whether the accelerant effect in vivo might be due partially to these circulatory changes.

The accelerants studied produced effects in the rat which varied from increased capillary permeability disappearing within 1–5 h (xylene, DMSO, di-2-ethylhexylamine), to local circulatory arrest, marked inflammation and necrosis (n-decylamine).

The mild effects were less marked after the histamine (H) and 5-hydroxy-tryptamine (5HT) contents of the skin had been lowered by treatment with compound 48/80 and reserpine respectively. Thus, the mild effects appeared to be due to the local release of H and 5HT. The necrosis caused by n-decylamine was not reduced by such procedures and was most likely due to its alkalinity and surface activity.

Neither H, Trafuril nor any of the accelerants tested increased the clearance of intradermally-injected radioactive ²⁴Na, and those accelerants which produced necrosis caused a marked and rapid reduction of the skin clearance of ²⁴Na.

It was concluded that the accelerant effect in vivo was due not to increased capillary permeability or transport away from the skin but solely to the increased permeability of the stratum corneum.