GUANETHIDINE AND PUPILLARY REACTION.
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Local application of guanethidine to the eye results in miosis. The sympathicolytic action of guanethidine on the pupil was proved by the consistent appearance of a Horner's syndrome after instillation of a 10% solution into the conjunctival sac. Lack of cocaine mydriasis and unimpaired adrenaline mydriasis after guanethidine application are further evidence of this mode of action. Guanethidine is the first drug that can be consistently relied upon to produce miosis by inhibiting sympathetic impulses to the intraocular pupillary muscles; it also inhibits sympathetic impulses to Horner's muscle of the upper lid. It is a reliable sympathicolytic agent for testing the reaction of abnormal pupils. (+info)
Acute colonic pseudo-obstruction: a pharmacological approach.
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Acute colonic pseudo-obstruction is a functional disorder that closely mimics mechanical large bowel obstruction, and in which inadvertent laparotomy carries a high mortality. Eleven such patients were treated by pharmacological manipulation of the autonomic innervation to the colon with guanethidine and neostigmine. Eight responded to treatment with passage of flatus and/or stool within 10 min with complete resolution of symptoms. In three patients the treatment failed. Postural hypotension occurred in only one patient and no other serious side-effect was apparent. This pharmacological approach to the management of acute colonic pseudo-obstruction is suggested as an alternative to the other treatment options of colonoscopic decompression or surgery, when conservative management has failed. (+info)
MODIFICATION OF THE EFFECTS OF GUANETHIDINE ON CARDIAC CATECHOL AMINES BY VARIOUS AGENTS.
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A study has been made of the effect of injections of guanethidine in rats, in depleting catechol amines from the whole cardiac ventricles and from various subcellular fractions. Unlike reserpine, guanethidine first affected the concentration of the amines in the soluble fraction of the cell. Neither [2-(2,6-dimethylphenoxy)-propyl]trimethylammonium chloride monohydrate (beta-methyl xylocholine) nor hemicholinium affected the endogenous catechol amines or the uptake of injected noradrenaline, but each significantly reduced the action of guanethidine in depleting catechol amines. Administration of choline chloride after hemicholinium reversed its influence on guanethidine depletion. In cats, cocaine potentiated the pressor response to noradrenaline, but antagonized the response to tyramine and guanethidine, while bretylium and N-o-chlorobenzyl-N'N"-dimethylguanidine sulphate (BW392C60) potentiated the responses to noradrenaline, tyramine and guanethidine. (+info)
COMPARISON OF THE EFFECTS OF BRETYLIUM, GUANETHIDINE AND BETHANIDINE ON SMOOTH MUSCLE RESPONSES TO DIFFERENT RATES OF SYMPATHETIC NERVE STIMULATION.
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The relative effects of bretylium, guanethidine and bethanidine on smooth muscle responses to different rates of sympathetic nerve stimulation have been compared. The responses studied were vasoconstriction in the femoral vascular bed and contraction of the spleen in anaesthetized cats, vasoconstriction in perfused ears of rabbits and inhibition of pendular movements in rabbit isolated ileum preparations. Except in the isolated ileum, the action of bretylium on curves relating the frequency of nerve stimulation and the effect on response was different from that of guanethidine. Whereas bretylium caused relatively greater inhibition of responses to high stimulus frequencies and depressed the slopes of the curves, guanethidine preferentially suppressed responses to low stimulus frequencies and caused roughly parallel shifts of the curves. In each situation tested bethanidine was the most potent of the three blocking agents and in general its effect on frequency/response curves was intermediate between those of bretylium and guanethidine. (+info)
Inhibition by adrenergic neurone blocking agents of the relaxation induced by BRL 38227 in vascular, intestinal and uterine smooth muscle.
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1. The adrenergic neurone blocking agents, guanethidine and bretylium, have been tested for inhibitory activity against the actions of some relaxant drugs (BRL 38227, noradrenaline, sodium nitroprusside, theophylline) in vascular, intestinal and uterine smooth muscle. 2. In guinea-pig isolated taenia caeci pre-contracted with KCl (25 mM), BRL 38227 (0.1-10 microM) and noradrenaline (10 nM-100 microM) each caused concentration-dependent relaxation. Guanethidine and bretylium (50 microM) each antagonized the relaxation to BRL 38227 but not that to noradrenaline. At high concentration (500 microM), the adrenergic neurone blocking agents antagonized the action of BRL 38227 and, to some extent, that of noradrenaline. 3. In rat isolated aorta pre-contracted with noradrenaline (300 nM), BRL 38227 (0.0125-3.2 microM) and sodium nitroprusside (0.3-100 nM) each produced concentration-dependent smooth muscle relaxation. Guanethidine and bretylium (5-500 microM) each antagonized the action of BRL 38227 without antagonizing that of sodium nitroprusside. 4. Rats were pretreated with 17-beta oestradiol benzoate. Tension waves were then induced from segments of isolated, oestrogen-dominated uterus by transmural electrical stimulation or by oxytocin (0.2 nM). These tension waves were inhibited by BRL 38227 (0.025-3.2 microM) or theophylline (0.05-0.8 mM) in a concentration-dependent manner. Guanethidine (50 microM) antagonized the action of BRL 38227 in both the electrically- and oxytocin-driven tissues. In the electrically-driven tissues, guanethidine (50 microM) did not antagonize the inhibition to theophylline. 5. In KCl (25 mM)-treated guinea-pig taenia caeci, guanethidine (50 microM) inhibited the efflux of 86Rb+ evoked by BRL 38227 (10 microM) but not that evoked by noradrenaline (10 microM). In contrast, apamin(100 nM) reduced the efflux of 86Rb+ which was promoted by noradrenaline, but did not affect efflux induced by BRL 38227.6. It is concluded that the adrenergic neurone blocking agents, guanethidine and bretylium (each at 50 microM), selectively inhibit the relaxant action of BRL 38227 in vascular, intestinal and uterine smooth muscle. If this inhibition reflects direct blockade of the K+-channel (KKCO) which is opened by BRL 38227, then the adrenergic neurone blocking agents act as inhibitors selective for KKCO as opposed to the small, apamin-sensitive (SKCa) and large (BKca) conductance, Ca2"-dependent K+-channels. (+info)
THE EFFECTS OF DRUGS ON THE UPTAKE OF AMINES BY MAST CELLS.
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Neoplastic mast cells, taken from an ascitic tumour in mice and incubated in vitro, took up (14)C-labelled 5-hydroxytryptamine and histamine from the medium. Uptake during the first hour gave an approximate measure of the initial rate. The amount of each amine taken up in this time was determined by bioassay and by radioactivity, the two methods giving similar results. The curves obtained by plotting initial rate of uptake against concentration in the medium suggested that the uptake of 5-hydroxytryptamine was by an active process and also by diffusion, whereas uptake of histamine was by diffusion only. The cells also took up (14)C-labelled (+/-)-noradrenaline and tryptamine, apparently by diffusion. The active uptake of 5-hydroxytryptamine was inhibited by lowering the temperature to 25 degrees C or by increasing the pH to 8.9, procedures which had little effect on histamine uptake. The effects of cocaine, imipramine, chlorpromazine, mepyramine, promethazine, phenoxybenzamine, lysergic acid diethylamide, bromolysergic acid diethylamide, methysergide, guanethidine, dichloroisoprenaline and pronethalol on the uptake of amines were examined. In general, any antagonist which inhibited uptake of 5-hydroxytryptamine had little effect on uptake of histamine, and vice versa. Possible ways in which these antagonists produce their effects on amine uptake are discussed. A high concentration of 5-hydroxytryptamine, of tryptamine or of noradrenaline inhibited uptake of histamine, but only tryptamine decreased uptake of 5-hydroxytryptamine. These results, together with those from experiments with antagonists, suggest that there are specific binding sites for 5-hydroxtryptamine in these cells. (+info)
SYMPATHOLYTIC DRUGS AND HYPERLIPAEMIA INDUCED IN RATS BY INTRAPERITONEAL INJECTIONS OF SURFACE-ACTIVE AGENT.
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Hyperlipaemia and hypercholesterolaemia were induced in white rats by intraperitoneal injections of tyloxapol. Various sympatholytics and adrenolytics, including blocking agents of beta-receptors, were given simultaneously with tyloxapol. Bretylium tosylate prevented the increase in the serum levels of esterified fatty acids and cholesterol caused by tyloxapol. Phentolamine decreased the enhancement by tyloxapol of cholesterol and total lipid concentrations in the serum. Guanethidine and phenoxybenzamine reduced the increase in the concentration of esterified fatty acids, whereas dichloroisoprenaline insignificantly increased the tyloxapol-induced hyperlipaemia. A small dose of pronethalol slightly increased the esterified fatty acid level in tyloxapol-treated animals; a large dose significantly decreased the serum cholesterol concentration. (+info)
AN ELECTROPHYSIOLOGICAL INVESTIGATION OF THE ACTIONS OF SOME AUTONOMIC BLOCKING DRUGS ON TRANSMISSION IN THE GUINEA-PIG VAS DEFERENS.
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Membrane potentials have been recorded from the guinea-pig isolated vas deferens with intracellular and sucrose-gap electrodes during stimulation of the hypogastric nerve and of intramural nerve fibres. Atropine had no detectable effect on the excitatory junction potentials in response to nerve stimulation or on the spontaneous discharge of small potentials. High concentrations of adrenolytic drugs, acting on alpha-receptors were needed to block the response to nerve stimulation and the spontaneous discharge. During the onset and recovery from yohimbine blockade, junction potentials in response to repetitive stimulation were not sustained. Bretylium initially reduced both the junction potentials and the spontaneous discharge. However, after 30 min exposure, the spontaneous discharge increased in frequency although the response to nerve stimulation was abolished. Block of the junction potentials by procaine was rapid in onset compared with that by bretylium and guanethidine, but the spontaneous discharge was not abolished. These results are discussed in relation to the mechanism of transmission from sympathetic nerve to smooth muscle. (+info)