Clinical Effects of Drugs Which Prevent the Release of Adrenergic Transmitter

Laurence, D. R.; Rosenheim, M. L.

doi:10.1002/9780470719206.ch20

Cited by 13 publications

(13 citation statements)

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“…Table 1 shows that such treatment reduces the ability of the heart slice to accumulate [3H1-noradrenaline and, to a lesser extent, [C 1]-guanethidine; similar findings for the accumulation of guanethidine have been reported previously (Brodie, Chang & Costa, 1965). Since amphetamine has been shown to be capable of releasing extragranularly bound noradrenaline (Lundborg & Waldeck, 1971;Farnebo, 1971) as well as reversing adrenergic nerve blockade (Laurence & Rosenheim, 1960;Follenfant & Robson, 1970), the agent was selected as a pharmacological tool to aid in relating noradrenaline binding and release characteristics to those of the adrenergic neuronal blocker, guanethidine. Amphetamine (10 gM) was found capable of releasing about 16% of the total…”

Section: Discussionsupporting

confidence: 74%

Extra‐vesicular Binding of Noradrenaline and Guanethidine in the Adrenergic Neurones of the Rat Heart: A Proposed Site of Action of Adrenergic Neurone Blocking Agents

Giachetti

Hollenbeck

1976

British J Pharmacology

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The binding and efflux characteristics of [14C]‐guanethidine and [3H]‐noradrenaline were studied in heart slices from rats which were pretreated with reserpine and nialamide. Binding of both compounds occurred at extra‐vesicular sites within the adrenergic neurone. After a brief period of rapid washout, the efflux of [14C]‐guanethidine and [3H]‐noradrenaline proceeded at a steady rate. The efflux of both compounds appeared to occur from a single intraneuronal compartment. (+)‐Amphetamine accelerated the efflux of [14C]‐guanethidine and [3H]‐noradrenaline; this effect was inhibited by desipramine. Unlabelled guanethidine and amantadine also increased the efflux of labelled compounds. Cocaine in high concentrations increased slightly the efflux of [14C]‐guanethidine but not that of [3H]‐noradrenaline. Heart slices labelled with [3H]‐noradrenaline became refractory to successive exposures to releasing agents although an appreciable amount of labelled compound was still present in the slices. It is suggested that [14C]‐guanethidine and [3H]‐noradrenaline are bound at a common extra‐vesicular site within the adrenergic neurone. Binding of guanethidine to the extra‐vesicular site may be relevant to its pharmacological action, i.e., the blockade of adrenergic transmission.

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Section: Discussionsupporting

confidence: 74%

Extra‐vesicular Binding of Noradrenaline and Guanethidine in the Adrenergic Neurones of the Rat Heart: A Proposed Site of Action of Adrenergic Neurone Blocking Agents

Giachetti

Hollenbeck

1976

British J Pharmacology

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“…In some patients treated with guanethidine hypotension is produced by exercise (Laurence & Rosenheim, 1960). This could be brought about if the effect of guanethidine were to abolish the adrenergic response to sympathetic nerve discharge and to replace it by a weak cholinergic response.…”

Section: Discussionmentioning

confidence: 99%

Effect of Guanethidine in Revealing Cholinergic Sympathetic Fibres

Day

Rand

1961

British Journal of Pharmacology and Chemotherapy

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Guanethidine abolished the inhibitory response of segments of rabbit intestine to stimulation of the sympathetic nerves which accompany the mesenteric arteries. In the majority of experiments a motor response of the intestinal segment was then revealed; it was more readily observed in intestinal segments from young than from adult rabbits. The motor response of the intestine to sympathetic stimulation after guanethidine was blocked by atropine. It was not blocked by hexamethonium and was present in rabbits in which the vagal innervation to the small intestine had been sectioned. In the cat isolated atria, guanethidine blocked the accelerator response to sympathetic nerve stimulation and revealed a response resembling that to stimulation of the vagus. It was concluded that guanethidine blocked the release of noradrenaline and thus revealed the response to the direct action of acetylcholine released from cholinergic sympathetic nerves.

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“…Clinical observations also indicate that amphetamine and related drugs specifically antagonize the hypotensive action of bretylium and guanethidine (Wilson & Long, 1960;Laurence & Rosenheim, 1960;Gulati, Dave, Gokhale & Shah, 1966).…”

Section: Discussionmentioning

confidence: 99%