Effect of Drugs on the Noradrenaline Content of Brain and Peripheral Tissues and Its Significance

Abstract

Large single doses of methoserpidine (12 mg/kg) given to rabbits lowered the noradrenaline content of sympathetic ganglia but not that of brain; no sedation was observed. Cats responded to doses ranging from 12 to 0.5 mg/kg with loss of noradrenaline from ganglia as well as from brain, and were sedated by the drug. The effect in man resembles that in the rabbit. Only within the group of reserpine-like drugs do sedation and loss in hypothalamic noradrenaline run parallel. These effects are therefore not causally related. Guanethidine lowers the noradrenaline content of sympathetic ganglia (cats and rabbits), but this effect does not explain the blocking action of the drug on the adrenergic nerve. Effects on the noradrenaline of the brain are variable and may be caused reflexly rather than by direct central action of guanethidine. Repeated intravenous injections of dimethylphenylpiperazinium iodide for a period of 4 hr did not produce any significant change in the noradrenaline content of ganglia or brain of rabbits. In contrast, dexamphetamine (20 mg/kg) produced a small but significant mean fall in noradrenaline content of the superior cervical ganglia and in that of the brain, but the effects were not seen in every rabbit. Prolonged administration of the mono-amine oxidase inhibitors pheniprazine and phenylhydrazinobutane raised the noradrenaline content of the brain of rabbits but not that of cats, whereas it raised the noradrenaline of the ganglia of cats but not (or rarely) that of rabbits. The question of correlation between a rise in the noradrenaline content of the brain and certain clinical signs is discussed. Finally, a comparison is made in rabbits between the changes produced by drugs in the noradrenaline content of the heart and of the superior cervical ganglion. The changes run parallel and are only occasionally more pronounced in the heart.A study was made of the changes-in the noradrenaline content of sympathetic ganglia and brain produced by a series of drugs. The first section deals with drugs which have pharmacological actions on different parts of the postsynaptic sympathetic neurones. Two of these drugs, methoserpidine (10-methoxydeserpidine) and guanethidine, cause hypotension, and the question arose whether this effect can be explained by changes in the noradrenaline content of the peripheral sympathetic neurones. A second point was to ascertain whether these drugs have any action on the brain. The actions of the two other drugs, the nicotine-like compound dimethylphenylpiperazinium iodide, which stimulates sympathetic ganglia, and

Role of noradrenaline in the acute pressor response to angiotensin in conscious cats

“…Thus, the pressor potency was reduced by treatment with the catecholamine depleting substances, reserpine and syrosingopine, and was restored by infusions of catecholamines. Similarly, inhibition of monoamine oxidase which has been shown to increase peripheral levels of catecholamines (Goldberg & Shideman, 1962;Sanan & Vogt, 1962) (Feldberg & Lewis, 1964, 1965Vane, 1969 (Bickerton & Buckley, 1961) and via central vagal inhibition (Scroop & Lowe, 1968). The failure of both pempidine and bethanidine to reduce the angiotensin pressor responses in the present experiments argues against a significant central component to the response.…”

Pharmacology of the Antihypertensive Guanoxan

“…It is ur'ilikely, in our opinion, that this was the result of a reflex mechanism, as was suggested by Sanan & Vogt (1962) to account for the small but significant decrease in the hypo-thalamic concentration of noradrenaline which they observed in rabbits treated with guanethidine. In the rabbit both guanoxan and guanethidine decreased the noradrenaline levels in peripheral tissues.…”

A neuronal basis for the alerting action of (+)‐amphetamine

“…Some biochemical studies have shown that high doses of amphetamine can lower the concentration of endogenous brain noradrenaline (McLean & McCartney, 1961;Moore & Lariviere, 1963;Baird & Lewis, 1964;Smith, 1965;Leonard & Shallice, 1971) but other studies have produced differing results (Sanan & Vogt, 1962;Breese, Kopin & Weise, 1970;Simon, Tillement, Larousse, Breteau, Guernet & Boissier, 1970). The significance of these findings is not clear as the doses of amphetamine used in these studies were in the lethal range (Stolk & Rech, 1968).…”