1967Journal of Pharmacy and PharmacologyRequires access

The accumulation of [3H]noradrenaline in the adrenergic nerve fibres of reserpine-treated mice

Arvid Carlsson, Bertil Waldeck

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Abstract

Abstract Mice, pretreated with reserpine, were given [3H]noradrenaline (3H-NA) intravenously and were killed 30 min later. Only small amounts of 3H-NA were recovered from the hearts. The monoamine oxidase inhibitor nialamide in a dose of 10 mg/kg increased the 3H-NA recovered from the hearts of reserpine-treated animals severalfold. In higher doses, however, this effect of nialamide was no longer observed. When 3H-NA was replaced by [3H]α-methylnoradrenaline, nialamide only reduced the amount of amine recovered from the hearts. The balance between the opposing actions of nialamide depended on dosage, time interval and temperature in a manner suggesting that the inhibitory influence was due to accumulation of endogenous amines in the adrenergic nerve fibres. Bretylium and harmaline also preserved 3H-NA in reserpine-treated animals whereas iproniazid, pheniprazine, pargyline and tranylcypromine did not do this. Moreover, pargyline blocked the ability of nialamide to enhance 3H-NA accumulation. The uptake of 3H-NA observed after monoamine oxidase inhibition in the hearts of reserpine-treated mice was almost completely blocked by pretreatment with desipramine or protriptyline, potent blockers of amine uptake by adrenergic nerve fibres.

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Abstract Mice, pretreated with reserpine, were given [3H]noradrenaline (3H-NA) intravenously and were killed 30 min later. Only small amounts of 3H-NA were recovered from the hearts. The monoamine oxidase inhibitor nialamide in a dose of 10 mg/kg increased the 3H-NA recovered from the hearts of reserpine-treated animals severalfold. In higher doses, however, this effect of nialamide was no longer observed. When 3H-NA was replaced by [3H]α-methylnoradrenaline, nialamide only reduced the amount of amine recovered from the hearts. The balance between the opposing actions of nialamide depended on dosage, time interval and temperature in a manner suggesting that the inhibitory influence was due to accumulation of endogenous amines in the adrenergic nerve fibres. Bretylium and harmaline also preserved 3H-NA in reserpine-treated animals whereas iproniazid, pheniprazine, pargyline and tranylcypromine did not do this. Moreover, pargyline blocked the ability of nialamide to enhance 3H-NA accumulation. The uptake of 3H-NA observed after monoamine oxidase inhibition in the hearts of reserpine-treated mice was almost completely blocked by pretreatment with desipramine or protriptyline, potent blockers of amine uptake by adrenergic nerve fibres.

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Available abstract

Abstract Mice, pretreated with reserpine, were given [3H]noradrenaline (3H-NA) intravenously and were killed 30 min later. Only small amounts of 3H-NA were recovered from the hearts. The monoamine oxidase inhibitor nialamide in a dose of 10 mg/kg increased the 3H-NA recovered from the hearts of reserpine-treated animals severalfold. In higher doses, however, this effect of nialamide was no longer observed. When 3H-NA was replaced by [3H]α-methylnoradrenaline, nialamide only reduced the amount of amine recovered from the hearts. The balance between the opposing actions of nialamide depended on dosage, time interval and temperature in a manner suggesting that the inhibitory influence was due to accumulation of endogenous amines in the adrenergic nerve fibres. Bretylium and harmaline also preserved 3H-NA in reserpine-treated animals whereas iproniazid, pheniprazine, pargyline and tranylcypromine did not do this. Moreover, pargyline blocked the ability of nialamide to enhance 3H-NA accumulation. The uptake of 3H-NA observed after monoamine oxidase inhibition in the hearts of reserpine-treated mice was almost completely blocked by pretreatment with desipramine or protriptyline, potent blockers of amine uptake by adrenergic nerve fibres.

Key concepts: Nialamide, Reserpine, Pargyline, Iproniazid, Chemistry, Monoamine oxidase, Endocrinology, Tranylcypromine

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