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Biomedical subjects

A L BOURA

Publications and source records attributed to A L BOURA.

14 recordsLinked to original sources
PubMed1963

Adrenergic neurone blockade and other acute effects caused by N-benzyl-N'N"-dimethylguanidine and its ortho-chloro derivative.

N-Benzyl-N'N"-dimethylguanidine sulphate (BW 467C60) and its ortho-chloro derivative (BW 392C60) had adrenergic neurone blocking and sympathomimetic effects resembling those of bretylium and guanethidine in cats, dogs and monkeys, but they were more potent in blocking adrenergic mechanisms in the cat. BW 467C60 was more active than its chloro derivative. Each compound inhibited release of noradrenaline during stimulation of the splenic nerve of cats, and increased smooth muscle responses to adrenaline and noradrenaline. Pressor responses to standard doses of tyramine were also increased except when large doses of BW 467C60 or BW 392C60 were given. The adrenergic neurone block by BW 467C60 was inhibited by dopamine, cocaine and amphetamine in situations in which these amines inhibit the effects of bretylium and guanethidine. In contrast to guanethidine, BW 467C60 and BW 392C60 did not lower the pressor amine content of the iris of cats 24 hr after administration of single doses of the compounds. BW 467C60 depressed the slope of curves relating the frequency of stimuli applied to the cervical sympathetic nerves and the resulting contraction of the nictitating membrane, but the effects of the lower rates of stimulation were preferentially inhibited. Large intravenous doses of BW 467C60 and BW 392C60 blocked autonomic cholinergic mechanisms and caused neuromuscular paralysis of voluntary muscle. These effects were brief, in contrast to the adrenergic neurone blockade. Both BW 467C60 and BW 392C60 were well absorbed from the alimentary tract. In contrast to guanethidine, BW 467C60 did not cause diarrhoea in guinea-pigs.

Adrenergic Agents↗
PubMed1962

Comparison of bretylium and guanethidine: tolerance, and effects on adrenergic nerve function and responses to sympathomimetic amines.

Bretylium depresses the slope of regression lines relating frequency of sympathetic nerve stimulation to magnitude of contractions of the cat nictitating membrane. In contrast, guanethidine and reserpine preferentially abolish responses to low rates of nerve stimulation and cause a roughly parallel shift of the regression lines. The hypersensitivity of the nictitating membranes of cats to intravenous adrenaline or noradrenaline is far greater after a series of small daily doses of bretylium or guanethidine than after single large doses. The maximal sensitivity produced was similar to that after postganglionic sympathetic nerve section and exceeded that produced by ganglion blockade. The development of hypersensitivity to catechol amines is accompanied by some return of responses of the nictitating membranes to sympathetic nerve stimulation despite continued daily administration of bretylium or guanethidine. In cats given bretylium daily, responses to low rates of nerve stimulation become greater than in controls unless the dose of bretylium given subcutaneously is 50 mg/kg or more. When marked hypersensitivity to catechol amines has been produced by giving bretylium or guanethidine daily for 7 or 14 days, the sympathomimetic effects of these compounds are greater. Responses to intravenous dimethylphenylpiperazinium are also increased and the results suggest that even large daily doses of adrenergic neurone blocking agents do not appreciably impair the functioning of the adrenal medulla. The pressor effects of intravenous adrenaline, noradrenaline and dimethylphenylpiperazinium iodide increase less than the corresponding nictitating membrane responses. These results are discussed in relation to tolerance to adrenergic neurone blockade, and differences between the effects of bretylium and guanethidine found in man. Bretylium and guanethidine depress the slopes of the dose-response curves for the pressor and nictitating membrane contracting effects of tyramine. When single doses or a short series of daily doses were given, guanethidine caused more depression of the slopes than did bretylium, but nevertheless large depressions of slope were found after giving bretylium daily for several weeks. The magnitude of the responses can be greater or less than in controls depending on the dose of the sympathomimetic amine, the dose of the adrenergic neurone blocking agent and the duration of its administration. The results suggest that injection of tyramine produces a progressively smaller release of adrenaline or noradrenaline during the daily administration of bretylium (or guanethidine) but that in some test situations this is more than compensated for by the development of hypersensitivity to the catechol amine released. Some corresponding changes in responses to amphetamine and ephedrine are also described.

Adrenergic Agents↗
PubMed1960

The selective accumulation of bretylium in sympathetic ganglia and their postganglionic nerves.

A study of the distribution of [(14)C]-labelled bretylium (N-o-bromobenzyl-N-ethyl-N,N-dimethylammonium) in cat tissues at various times after subcutaneous injection suggests that the specificity of its blocking action on adrenergic neurones may be related to its selective accumulation in these neurones. The rate of rise and fall of concentration in sympathetic ganglia and postganglionic sympathetic nerves showed a close similarity to the time course of the blocking adrenergic neurones as manifested by relaxation of the nictitating membranes. Concentrations found were similar to those in adrenergic nerve trunks when topical application of the drug had caused a local block of conduction. Conduction in other types of nerve could be blocked by topical application, but in general they were less sensitive, heavily myelinated nerves being the most resistant.

Animals↗
PubMed1959

The actions of bretylium: adrenergic neurone blocking and other effects.

Bretylium caused a specific and lasting depression of many excitatory and inhibitory responses evoked by electrical stimulation of the peripheral sympathetic nervous system, probably by impairing conduction of impulses in adrenergic neurones with consequent failure of noradrenaline and adrenaline release. This effect, which will be referred to as the adrenergic neurone blocking action, was preceded by weak sympathomimetic effects. In the presence of bretylium the effects of adrenaline and noradrenaline were increased, as after sympathectomy. Concentrations producing blocking of adrenergic neurones did not prevent the release of adrenaline and noradrenaline from the adrenal medulla by splanchnic nerve stimulation or by the injection of dimethylphenylpiperazinium iodide, nor did they cause antiparasympathetic or parasympathomimetic effects. No action on the central nervous system has been detected. Curare-like neuromuscular block occurred with 10 to 30 times the amount required to block the response to adrenergic nerve stimulation alone and was accompanied by signs of temporary synaptic block in autonomic ganglia. Adrenergic nerve trunks and sensory nerves in the skin were readily blocked for long periods by topical application of bretylium, whereas the phrenic nerve of the rat was not. Bretylium had little effect on gastrointestinal propulsion or on the sensitivity of smooth muscle to acetylcholine, 5-hydroxytryptamine, adrenaline, or noradrenaline, but moderate amounts depressed the peristaltic reflex and the sensitivity of the guinea-pig ileum to histamine. Bretylium caused postural hypotension in the cat in doses which had little effect on the supine blood pressure. Experiments on the nictitating membrane indicated that compensation for the effects of bretylium on low rates of stimulation of postganglionic sympathetic nerves could be attained by a small increase in the rate of stimulation, whereas compensation for its effects on high rates required an increase in the rate of stimulation beyond physiological limits.

Acetylcholine↗