Effect of Amine Uptake Inhibitors on the Uptake of 14C‐Bretylium in Intact and Degenerating Sympathetic Nerves of the Rat

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Abstract: The effect of different amine uptake inhibitors on the accumulation of 14C‐bretylium in sympathetically denervated or decentralized salivary glands were studied in vivo rats 11–14 hours after the surgical intervention. The time period chosen is known to be critical for the delaying effect of bretylium on the degeneration transmitter release in sympathetically innervated organs. Cocaine, desmethylimipramine (DMI), protriptyline or reserpine all depressed the uptake of 14C‐bretylium in both denervated and decentralized salivary glands, cocaine being the most efficient one. DMI and protriptyline, but not cocaine inhibit the degeneration delaying effect of bretylium, while all three agents inhibit amine uptake at level of the nerve cell membrane. Apparently, bretylium reaches the critical sites of its degeneration delaying action by the axonal amine pump but only a small fraction of the drug entering the degenerating adrenergic nerve terminal is needed at the critical sites to interact with the degeneration processes. The difference between the tricyclic antidepressants on one hand and cocaine on the other with respect to the effect on the degeneration delaying action of bretylium, must depend on some action different from the axonal membrane uptake inhibition. Reserpine which is known not to interfere with the delaying effect of bretylium on the denervation degeneration did reduce the uptake of, 14C‐bretylium. This fact seems to indicate that the site of action of bretylium is located outside the adrenergic nerve granules.