Determination of Guanethidine in Sympathetic Ganglia

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Abstract
Guanethidine sulphate was administered intraperitoneally in a dose of 10‐60 mg/kg for up to two months to adult male rats and the content of guanethidine in the superior cervical ganglia was determined fluorometrically after combination with ninhydrin in alkaline solution. Guanethidine was shown to concentrate in the superior cervical ganglia. Twenty four hours after the discontinuation of guanethidine sulphate 20 mg/kg for 14 days, the mean total gang‐lionic content of guanethidine base was 50 ng/ganglion (S.D. 8.8, n = 10) corresponding to 83 μg/g dry weight or 17 μg/g wet weight. Following a single injection of guanethidine sulphate and following discontinuation of prolonged administration of the drug the ganglionic guanethidine declined with a half‐life of 35 hours. Most of the ganglia were excised 24 hours after discontinuation of administration of the drug at which time the decline in ganglionic guanethidine was exponential. Desmethylimipramine largely prevented the accumulation of guanethidine in the ganglia indicating a mainly intraneuronal localization of guanethidine, a localization which was confirmed by microautoradiography. Reserpine only lowered the content to a small extent possibly indicating a mainly extragranular localization of guanethidine in the nerve cells. The selective morphological effects of guanethidine on sympathetic ganglia previously demonstrated were almost completely prevented by desmethylimipramine but only to a small extent by reserpine. SKF‐525‐A potentiated the ganglionic effects of guanethidine. It is assumed that the ganglionic effects are due to a cytotoxic effect of guanethidine concentrating selectively in the sympathetic ganglion nerve cells with the major part being located outside the noradrenaline storage granules as opposed to a mainly intragranular localization in the peripheral sympathetic terminals.