Uptake and Retention of 14C-Bretylium in Degenerating Postganglionic Sympathetic Nerves of the Rat

The uptake and retention of 14C-bretylium was studied in rat salivary glands and irides in vivo at different time intervals after sympathetic denervation or decentralization. The uptake of bretylium was increased on the denervated side during a time period which precedes the degeneration release of sympathetic transmitter, but was later on reduced. On the other hand, the retention of bretylium on the denervated side was already markedly reduced during the time period preceding the onset of the degeneration transmitter release. In experiments with chronically denervated salivary glands, or glands atrophied by means of excretory duct ligation, a pronounced extraneuronal accumulation was observed. The extraneuronal accumulation of bretylium may partly mask the changes in disposition of the drug induced by the sympathetic denervation. The results are in accordance with the hypothesis that bretylium must be associated with special sites at the adrenergic nerve terminals in order to exert its degeneration delaying effect.