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At least 19 recordsLinked to original sources
PubMed1979

Evaluation of a 5% guanethidine and 0.5% adrenaline mixture (Ganda 5.05) and of a 3% guanethidine and 0.5% adrenaline mixture (Ganda 3.05) in the treatment of open-angle glaucoma.

A trial of a mixture of guanethidine 5% and adrenaline 0.5% (Ganda 5.05) and of guanethidine 3% and adrenaline 0.5% (Ganda 3.05) was conducted on 90 eyes in 53 patients with open-angle glaucoma or ocular hypertension. The cases fell into 5 groups: untreated cases, cases on pilocarpine 1%, on pilocarpine 2%, on pilocarpine 2 to 4% and adrenaline 1%, and on separate guanethidine 5% and adrenaline 1%. Baseline pressures and average pressures on the previous treatment were established. Substitution with Ganda 3.05 or 5.05 was started, and the patients attended 2 weeks, 1 month, 3 months, and 6 months from the start of the trial. Applanation tonometry was carried out at the same time of day. The pupil was measured, ptosis and superficial punctate corneal staining were looked for and evaluated, and the patients were questioned for symptoms of side effects and acceptability. All the eyes that had previously been treated with pilocarpine 1% or 2% presented significantly lower intraocular pressures on Ganda 3.05. The patients on pilocarpine 4% and adrenaline 1% also had lower intraocular pressures on Ganda 5.05, but the significance was less, and the patients on separate guanethidine and adrenaline had a small but not statistically significant drop in pressure. Ptosis and discomfort were evaluated on a subjective scale. Patient acceptability was good. The trial was interrupted in 5 cases for various reasons. Tachyphylaxis and tolerance to the mixtures were not observed in this series.

Clinical Trials as Topic↗
PubMed1992

Effect of immunosuppressive agents on the guanethidine-induced sympathectomy in athymic and euthymic rats.

Guanethidine sulphate causes destruction of peripheral sympathetic neurons and infiltration of mononuclear inflammatory cells in the sympathetic ganglia of both athymic nude (rnu/rnu) and euthymic LEW/Mol rats. The effect of guanethidine is believed to be an autoimmune reaction. To determine the effect of immunosuppressive drugs concurrently with guanethidine treatment both athymic and euthymic rats were treated with guanethidine 40 mg/kg i.p. daily for 14 days, cyclophosphamide 100 mg/kg i.p. on days 1 and 8, methylprednisolone 10 mg/kg and cyclosporin A 10 mg/kg daily from days 1 to 7, and then every other day from days 8 to 14. The number of neurons in the sympathetic ganglia was counted and four subpopulations of mononuclear inflammatory cells were identified by monoclonal antibodies MHC II, CD8 T-cells/NK-cells, CD5 T-cells, CD4 T-cells/macrophages. Our results show that the immunosuppressive drugs used were unable to prevent the guanethidine-induced reduction of sympathetic neurons, although the number, of neurons following guanethidine-methylprednisolone treatment was significantly higher compared with guanethidine alone in both athymic and euthymic rats. The identification of mononuclear cells in the sympathetic ganglia showed that the CD8/NK and CD5 populations were the populations primarily responding to guanethidine treatment. Both CD8/NK and CD5 populations were absent without guanethidine, but increased significantly following guanethidine in both athymic and euthymic animals. None of the immunosuppressive drugs used could prevent the guanethidine-induced rise in the CD8/NK population in neither athymic nor in euthymic rats. The rise in the CD5 population was suppressed following treatment with all immunosuppressive drugs in athymic rats, but only following methylprednisolone in euthymic animals. These results indicate that guanethidine induces proliferation of T-cells in euthymic rats and non-functional CD5 positive pre T-cells in athymic animals. The CD5 population in both athymic and euthymic animals appears relatively more sensitive to immunosuppressive drugs than the NK-cell population also activated by guanethidine. This relatively resistant NK-cell population seems to play an important role in the guanethidine-induced destruction of sympathetic neurons and can explain why the guanethidine-induced immunological reaction could not be fully prevented by the immunosuppressive drugs used. The conclusion is that guanethidine induces destruction of sympathetic neurons by a NK-cell-mediated reaction.

Animals↗
PubMed1977

Guanethidine-induced acute hypersensitivity to noradrenaline in anaesthetized rats.

The changes in mean arterial blood pressure, heart rate and the respective noradrenaline dose-response curves after guanethidine sulphate (0.25, 1.25, 5, 20, and 40 mg/kg given intravenously) were studied in chloralose-urethane anesthetized adult rats. After transient changes a dose-dependent maximum fall of the blood pressure was observed 15 minutes after the administration of guanethidine. A fall in heart rate was observed after guanethidine sulphate 0.25 mg/kg, whereas 1,25, 5, 20, and 40 mg/kg initially increased the heart rate followed by a decrease to subnormal levels with minimum values 6-24 hours after guanethidine. Normalization of blood pressure and heart rate occurred within 24 hours and 96 hours, respcetively. Maximum dose-dependent enhancement of changes in blood pressure by noradrenaline 0.5 mug/kg was obtained approximately 15 minutes after guanethidine. Following guanethidine 40 mg/kg the response was increased by a factor 2, and normalization occurred within 96 hours. Fifteen minutes after guanethidine, significant changes in the response of the heart rate to noradrenaline 0.5 mug/kg were obtained with guanethidine 1.25, 5, and 20 mg/kg, whereas fully developed hypersensitivity after 20 and 40 mg/kg did not occur until 6-24 hours later. Following guanethidine 40 mg/kg the response was increased by a factor of 3, and normalization was observed after 96 hours. The present investigation has demonstrated different time-dependent patterns of the effect of guanethidine on blood pressure and heart rate responses to noradrenaline.

Animals↗
PubMed1977

Guanethidine induced sympathectomy in the adult rat. II. Functional effects following chronic administration.

Guanethidine sulphate in doses of 5 and 40 mg/kg was administered intraperitoneally to adult rats daily for three months followed by discontinuation of administration for one day or three months. Following guanethidine 40 mg/kg a loss of approximately 95% of the nerve cells of the superior cervical ganglion was observed. No changes were observed after 5 mg/kg. The average mean arterial blood pressure (measured under chloralose-urethane anaesthesia) was lowered by 33 and 54 mmHg by guanethidine 40 mg/kg for three months followed by discontinuation for one day and three months respectively. The heart rate was unchanged. Guanethidine 5 mg/kg did not change any of these parameters. The increase in blood pressure and heart rate caused by intravenously administered noradrenaline was greatly enhanced following guanethidine 40 mg/kg, whereas only small changes were observed following 5 mg/kg. Following discontinuation for one day of 40 mg/kg for three months the potency ratios for the mean arterial blood pressure and the mean heart rate were 31 and 21 respectively, after discontinuation for three months 44 and 17 respectively. The potency ratios following guanethidine 5 mg/kg were 1.5 to 2.0. No changes were observed in the weight of the suprarenal glands following guanethidine. The present investigation has demonstrated an almost total chemical sympathectomy by guanethidine 40 mg/kg for three months and a persistent hypersensitivity to noradrenaline even after discontinuation of medication for three months.

Animals↗
PubMed1979

Unique resistance to guanethidine-induced chemical sympathectomy of spontaneously hypertensive rats: a resistance overcome by treatment with antibody to nerve growth factor.

The chronic administration of high doses of guanethidine to rats produces complete destruction of the peripheral sympathetic nervous system. In a study of the effect of guanethidine-induced sympathectomy on the development of hypertension is spontaneous hypertensive rats (SHR, Okomoto strain), only a partial sympathectomy could be produced as assessed by biochemical parameters (tyrosine hydroxylase activity in ganglia and tissue norepinephrine concentrations) and by evaluation of response to stimulation of vasomotor outflow in pithed rat preparations. Other strains of rats (Sprague-Dawley, American Wistar, Kyoto Wistar) were uniformly sensitive to guanethidine sympathectomy. The resistance to guanethidine was not due to a lower accumulation of guanethidine in the neurons of SHR. Addition to the guanethidine treatment of low doses of antibody to nerve growth factor (NGF), which itself produced only a modest sympathectomy, resulted in an almost complete sympathectomy. SHR did not become hypertensive when sympathectomized by combined guanethidine-anti NGF. These results show that the sympathetic neurons of SHR differ from those of other strains with respect to sensitivity to guanethidine cytotoxicity and suggest the possibility of a role for NGF in that altered responsiveness.

Animals↗
PubMedDate not supplied

Effects of chronic intracranial injection of low and high concentrations of guanethidine in the rat.

Low (64 mug in 2 mul) or high 320-1280 mug in 2 mul) doses of guanethidine sulphate were injected daily for up to 19 days into the lateral hypothalamus, substantia nigra, locus coeruleus, dorsal raphe nucleus, or amygdala region of the rat brain. Effects on monoamine-containing neurons were determined using fluorescence histochemistry. The noradrenergic terminals of the hypothalamus were depleted over a diameter of 7 mm by both low and high doses of guanethidine whereas, even with high doses, the dopaminergic terminals of the median eminence, amygdala and acudate nucleus were only partially depleted. Fluorescence levels of dopaminergic cell bodies of the sub stantis nigra and 5HT-containing cell bodies of the dorsal raphe nucleus were unaltered by low doses of guanethidine. Low doses of guanethidine did not affect the fluorescence of the noradrenergic cell bodies of the locus coeruleus, however high doses caused a substantial reduction in fluorescence levels. Normal levels of fluorescence were observed in all catecholamine-containing neurons within 14 days from cessation of injections. Thus, the xon retraction and eventual degeneration of peripheral sympathetic adrenergic neurons, which occurs as a result of chronic intraperitoneal injections of guanethidine does not occur with the catecholamine-containing neurons in the central nervous system. The rapid recovery of centrat catecholamine-containing neurons is remarkable in view of the extensive areas of brain damage produced by chronic injection of such high concentrations of drug. Fluorescence in peripheral adrenergic nerves was unaffected by chronic injection of guanethidine into the lateral hypothalamus but adhesions of some internal organs were observed. Blood vessels in the vicinity of the cannula were heavily reinnervated by fluorescent fibres probably arising from intracranial catecholamine-containing neurons. Some of the advantages of intracranial injection of guanethidine compared to 6-hydroxydopamine for behavioral experiments are discussed.

Amygdala↗
PubMed1978

Action of guanethidine on rabbit atrial membranes.

1 Intracellular potentials were recorded in driven left atria from reserpine-treated rabbits. Guanethidine 2 X 10(-5) M slightly increased Vmax and shortened the total duration (TD) of the action potential (AP) without causing hyperpolarization. For the first 30 min after 4 X 10(-4) M, Vmax increased without hyperpolarization and AP height increased slightly. Thereafter, Vmax and height decreased with a slight and gradual depolarization. This depolarization was irreversible. TD was increased after 15 minutes. Guanethidine 2 X 10(-3) M initially decreased Vmax and height before causing depolarization. 2. Pretreatment with tetrodotoxin (TTX) 1.6 X 10(-7) M prevented or reversed the initial increases in Vmax, height and TD induced by guanethidine (4 X 10(-4) M). 3 TTX 3.1 to 6.2 X 10(-6) M, added 15 or 30 min after guanethidine 4 X 10(-4) M, delayed or prevented depolarization by guanethidine. 4 Ouabain 10(-5) M incubated for 20 and 90 min greatly inhibited Na+, K+-adenosine triphosphatase and K+-phosphatase activities; guanethidine was without effect. 5 Guanethidine probably increases resting sodium permeability after the promotion of increases in sodium permeability during the AP. High doses of the drug decrease sodium permeability during the AP.

Adenosine Triphosphatases↗
PubMed1977

Guanethidine induced sympathectomy in the adult rat. I. Functional effects following subacute administration.

Guanethidine sulphate 5 and 40 mg/kg was administered intraperitoneally to adult rats for 4, 8, 14, and 28 days followed by discontinuation for 1 day, after administration for 28 days and additionally for 8, 14, 29, and 60 days. Under chloralose-urethane anaesthesia the mean arterial blood pressure and the mean heart rate were determined and the response of these parameters to intravenous noradrenaline 3-1600 ng was recorded. The blood pressure was not significantly changed after guanethidine 5 mg/kg, but lowered by 40 mg/kg, the decrease being reversible on discontinuation. The response of both parameters to noradrenaline was increased by guanethidine depending on the dose. The hypersensitivity was partly reversible on discontinuation, but a significantly increased sensitivity of the heart rate to noradrenaline was observed 60 days after discontinuation of guanethidine 40 mg/kg for 28 days. Histologically a profound loss of nerve cells of the superior cervical ganglion was observed following guanethidine 40 mg/kg, whereas no change was observed after 5 mg/kg. The present investigation has demonstrated that guanethidine 5 mg/kg does not induce histological or permanent haemodynamic changes, whereas 40 mg/kg for 28 days result in an incomplete sympathectomy accompanied by a partially irreversible hypersensitivity to noradrenaline. There is no simple relation between the loss of ganglion cells and the haemodynamic changes, and hence the hypersensitivity to noradrenaline is only in part due to the destruction of the postganglionic sympathetic neurone obtained by long term administration of large doses of guanethidine.

Animals↗
PubMed1977

Multiclinic controlled trial of bethanidine and guanethidine in severe hypertension.

One hundred and eight patients with initial diastolic blood pressure in the range of 100-124 mm Hg while taking hydrochlorothiazide were assigned randomly and double-blind to hydrochlorothiazide plus either bethanidine or guanethidine. The average reduction of the fifth and sixth months' diastolic blood pressure was 18.4 mm Hg for guanethidine and 13.6 mm Hg for bethanidine (P less than 0.01). The distribution of the individual values was such that 68.8% of guanethidine treated patients achieved a diastolic level below 90 mm Hg, compared to only 45.5% of the bethanidine treated group (P less than 0.025). The degree of orthostatic fall in blood pressure was greater with bethanidine than with guanethidine (P less than 0.05). The diurnal variation of blood pressure was slightly greater with bethanidine than with guanethidine. The results significantly favor guanethidine. This study failed to demonstrate that the shorter action of bethanidine confers significantly better control of blood pressure than the longer action of guanethidine.

Bethanidine↗
PubMed1975

Comparison of the effects of intracranial injections of 6-OHDA and guanethidine on consummatory behavior and monoamine depletion.

6-Hydroxydopamine (6-OHDA) has been used extensively to study the effects of catecholamine depletion on feeding and drinking behavior. The results from these experiments are variable and do not clarify the involvement of catecholamines in these behaviors. Guanethidine, which has been used in studies of the peripheral autonomic nervous system, provides an alternative method of catecholamine depletion. In the experiments reviewed here the effects of injections of 6-OHDA and guanethidine into the rat brain on consummatory behavior and temperature regulation have been compared and related to changes in monoamine levels as shown by fluorescence histochemistry. Injections of 6-OHDA into anterior hypothalamic areas have lethal effects on food deprived animals. This effect may be explained in terms of loss of ability to regulate temperature. Animals whose catecholamines were depleted by guanethidine injections into anterior lateral hypothalamus showed a consistent reduction in food and water intake and an elevation of body temperature. Reconciliation of these findings appears difficult. However, a comparative study of the intracranial diffusion patterns of guanethidine and 6-OHDA has revealed marked differences in the extent of diffusion as seen with the fluorescence histochemical method when injected acutely or chronically into the lateral hypothalamus, the substantia nigra or the amygdala of the rat brain. Cannulation damage extended up to 1 mm in diameter. Generalized damage was far greater for 6-OHDA (2 mm) than for guanethidine (0.3 mm). At the doses used guanethidine, but not 6-OHDA caused specific damage to catecholamine-containing neurons up to a distance of at least 3 mm from the cannula tip. Guanethidine was less selective for dopaminergic compared to noradrenergic neurons. These differences between the effects of the two drugs are explained in terms of their unique pharmacological properties and their estimated decay in CNS tissue. An attempt has been made to account for the differences in behavioral data and in particular the variability of the 6-OHDA data in terms of the differences in the type of damage produced by the two drugs and the extent of their diffusion. It is also argued that the different patterns of damage would not easily be distinguished by biochemical analysis, and further, that changes in injection volume and concentration may lead to different damage patterns.

Amygdala↗
PubMed1975

Biochemical and functional evaluation of the sympathectomy produced by the administration of guanethidine to newborn rats.

The administration of guanethidine to newborn rats has been shown by morphological criteria to destroy sympathetic neurons. Newborn rats were injected with guanethidine (50-100 mg/kg/day for 20 days). Upon maturation (at 10 weeks old), the degree of destruction of the sympathetic nervous system (sympathectomy) was assessed. Marked decreases (80-98%) in the norepinephrine concentration in several tissues (heart, spleen, intestine, mesentery, kidney, uterus, vas deferens) were observed in the guanethidine-treated rats when compared to saline-treated controls. No changes were observed in the epinephrine concentration in the adrenals or in the norepinephrine levels in whole brain. Analysis of brain areas showed no change in the norepinephrine levels in brain stem and cerebrum and a small (18%) decrease in the cerebellum. Stimulation of the sympathetic vasomotor outflow in the pithed rat preparation produced almost no response in guanethidine-treated animals. Periarterial nerve stimulation of the isolated perfused kidney preparation also produced essentially no response in guanethidine-treated animals. Isolated intestinal preparations from guanethidine-treated animals responded to nerve stimulation with contractions rather than relaxation as seen in preparations from control animals. Isolated vas deferens preparations responded normally to nerve stimulation despite a 95% decrease in tissue norepinephrine concentration. These data indicate that administration of guanethidine to newborn rats produces a more complete peripheral sympathectomy, especially of the vasculature, than immunosympathectomy or neonatal administration of 6-hydroxydopamine and does so with no significant effect on central noradrenergic neurons.

Adrenal Glands↗
PubMed1975

The relationship of plasma guanethidine levels to adrenergic blockade.

Seventeen hypertensive patients receiving guanethidine for therapy were studied to determine the relationship of guanethidine plasma levels to adrenergic blockade. Plasma levels of guanethidine were measured by gas chromatography-mass spectrometry, and adrenergic blockade was defined by determining the venous reflex response to Valsalva maneuver or deep breath. A significant correlation was found between the change in the venous reflex response and the fall in mean standing pressure when guanethidine is given to patients maintained on a sodium restricted diet. A linear relationship was found between dose and plasma guanethidine concentration (p less than 0.0001), but there was a 6-fold interindividual variation in the plasma levels resulting from any given dose. Adrenergic blockade occurred when plasma levels were 8 ng/ml or higher. These results indicate that the large individual variation in dose requirements for the hypotensive effects of guanethidine most likely is not due to requirements for greatly different plasma levels of the drug; that the variation must result from pharmacokinetic determinants of differing plasma levels between individuals or from other factors, such as increased plasma volume, which maintain elevated arterial pressure in the face of adrenergic blockade.

Adrenergic alpha-Antagonists↗
PubMed1977

Sympathetic blockade of isolated limbs by intravenous guanethidine.

As a result of experience at the Montreal General Hospital, it has been found that intravenous guanethidine blockade of extremities has therapeutic, prophylactic and diagnostic value in conditions where the aetiology is a disorder of sympathetic nervous conduction. The properties of guanethidine, namely its selective action on blocking the sympathetic nervous system peripherally, together with its long half time and rapid tissue fixation, render it a very useful drug in techniques where an isolated limb is blocked with guanethidine. Experience on a 18-month basis suggests that the procedure of intravenous guanethidine blockade offers exceptionally good results for a non-invasive technique. Work is now in progress to study the possible use of guanethidine in the treatment of phantom limb pain, and also to see whether other drugs, such as thymoxamine, could be used in a similar fashion to guanethidine.

Anesthesia, Intravenous↗
PubMed1976

Time-course effects of oral guanethidine administration on cardiovascular and autonomic effects on dogs.

The time-course effects of guanethidine (2.5 mb/kg/day, p.o.) administered for 2 days, 7 days and 7-8 months were investigated in dogs. Guanethidine treatment for 2 days failed to produce any significant alterations in sympathetic neuronal activity to the myocardium, resting neurogenic tone in the perfused hind limb vasculature and lumbar sympathetic neuronal transmission. Following guanethidine administration for a peroid of 7 days both cardiac and lumbar sympathetic neuronal activity was markedly and significantly depressed with concomitant reduction in heart rate and resting neurogenic tone to the hind limb. However, continued treatment with guanethidine for a period of 7-8 months resulted in complete restoration of cardiac as well as lumbar sympathetic neuronal activity. Both heart rate and resting neurogenic tone were also returned to placebo levels. The development of tolerance of these sympathetic nerves to guanethidine treatment was not associated with any alterations in the activity of adrenergic receptors. Further, there was a significant and time-dependent increase in cholinergic vasocilator activity in the lumbar sympathetic chain which could account for the exertional hypotension noted in the patients receiving guanethidine treatment.

Administration, Oral↗
PubMed1976

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.

1 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. 2 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. 3 (+)-Amphetamine accelerated the efflux of [14C]-noradrenaline; this effect was inhibited by desipramine. 4 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. 5 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 in these slices. 6 It is suggested that [14C]-guanethidine and [3H]-noradrenaline are bound at a common extravesicular 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.

Amphetamine↗
PubMed1978

Guanethidine-induced vasodilatation in the rabbit, mediated by endogenous histamine.

1 The effects of guanethidine (0.5-4 mg/kg i.v.) on arterial pressure, hindlimb blood flow and hindlimb vascular resistance (HVR) were studied in unanesthetized rabbits subjected to "total" autonomic block. 2 Evidence that this response was mediated by histamine release was that (a) 3H-labelled histamine levels in the hindlimb venous blood rose substantially after guanethidine; (b) infusion of exogenous histamine caused an inhibition of the guanethidine-induced vasodilatation; and (c) competitive antagonism of the response was obtained with the H2-antagonist burimamide. 3 There was good correlation between the [3H]-histamine ;elease and the time course of the vasodilator response. Glyceryl trinitrate infusions that lowered HVR substantially, did not cause release of histamine. 4 Reserpine, desipramine and indomethacin pretreatment did not alter the vasodilator response to guanethidine. 5 The guanethidine vasodilator response was not influenced by the H1-antagonist mepyramine or by the other H2-antagonists, metiamide or cimetidine. The vascular receptors stimulated by endogenous histamine may be distinctive from those stimulated by exogenous histamine, or the action of guanethidine may involve greater production of histamine at an intracellular site that is more readily reached by burimamide than by the other H2-antagonists.

Animals↗
PubMed1978

Prevention by guanethidine analogues of output of noradrenaline induced by sodium reduction in rabbit ventricular slices.

1 The prevention by guanethidine and related agents of the output of noradrenaline induced by low sodium was investigated in rabbit ventricular slices. When external NaCl was reduced, the output of noradrenaline into the medium collected at 30 min intervals, increased and the endogenous levels decreased. These changes induced by replacing sodium with sucrose or choline were not affected either by the omission of calcium and addition of 0.5 mM ethylene glycol-bis(aminoethylether)N,N,N',N' tetra-acetic acid (EGTA) or by an increase in the calcium concentration to 10 mM 30 min before sodium deprivation.2 Guanethidine 4 x 10(-6) and 4 x 10(-5) M and 4-7-exo-methylene-hexahydroisoindoline-ethyl guanidine (No. 865-123) 4 x 10(-5) to 8 x 10(-4) M inhibited, in a dose-dependent manner, increases in output of noradrenaline induced by reduction of sodium to 18 mM, while guanethidine 8 x 10(-5) M and high doses of bretylium produced no inhibition: the latter two released noradrenaline.3 The inhibitory actions of guanethidine 4 x 10(-5) M and No. 865-123 4 x 10(-4) M were prevented by tetracaine 3.3 x 10(-4) M, which per se did not modify the output of noradrenaline induced by 18 mM sodium.4 Accumulation of guanethidine and No. 865-123 in ventricular slices was greater than that noted in striated muscle slices and was dose-, time- and temperature-dependent. Tetracaine 3.3 x 10(-4) M did not prevent the accumulation of guanethidine 4 x 10(-5) M and No. 865-123 1.1 x 10(-6) to 4 x 10(-4) M.5 The guanidine derivatives appear to increase the permeability of adrenergic nerve endings to sodium ions.

Animals↗
PubMed1979

Relationship between accumulation, storage and overflow of noradrenaline in the rat salivary gland after chronic treatment with guanethidine.

1 The effect of guanethidine on the endogenous noradrenaline (NA) content, accumulation and overflow of [3H]-noradrenaline ([3H]-NA) in the rat salivary gland was examined at various times after drug administration. 2 Twenty-four h after a single injection of guanethidine (1 or 10 mg/kg s.c.), the respective values for the endogenous NA content and for the accumulation and overflow of [3H]-NA were approximately 55, 85, 30%, and 15, 55, 10% of the controls. 3 Although [3H]-NA accumulation had returned to control levels within 48 h after the dose of 10 mg/kg guanethidine, the overflow of [3H]-NA evoked by electrical stimulation or excess potassium (K+) remained depressed. 4 After the low or the high dose of guanethidine, the NA content of the salivary gland was restored to about 50% of the normal value between 4 to 24 and 48 to 72 h, respectively. 5 The accumulation of [3H]-NA was inhibited by about 75% by cocaine. The same degree of inhibition was obtained 4 h after 10 mg/kg guanethidine. In these experiments phenoxybenzamine did not reduce the residual (25%) uptake. 6 The reasons for differential rates of recovery of the endogenous NA content and the storage of [3H]-NA after guanethidine are discussed.

Animals↗