Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GUANETHIDINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1995

Intravenous regional guanethidine in the treatment of reflex sympathetic dystrophy/causalgia: a randomized, double-blind study. Guanethidine Study Group.

This double-blind, randomized, multicenter study was designed to determine the short-term and long-term efficacy of intravenous regional block with guanethidine in patients with reflex sympathetic dystrophy (RSD)/causalgia. Sixty patients were enrolled to receive four intravenous regional blocks at 4-day intervals with either guanethidine or placebo in 0.5% lidocaine. Each patient was randomized to receive either one, two, or four blocks with guanethidine. Follow-up visits were scheduled for 4 days, 1 mo, 3 mo, and 6 mo after their final block. At 4 days after the initial block, the group treated with placebo experienced a greater decrease in pain scores than those treated with guanethidine, although this difference was not statistically significant. On long-term followup there was no difference in pain scores between groups receiving one, two, or four guanethidine blocks. Overall, only 35% of patients experienced clinically significant relief on long-term followup even though all were treated early in the evolution of RSD.

Adult↗
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↗
PubMed2002

The effect of guanethidine and local anesthetics on the electrically stimulated mouse vas deferens.

UNLABELLED: Complex regional pain syndrome is often treated with the sympatholytic guanethidine and a local anesthetic in a Bier's block. The efficacy of this treatment has been questioned. Because local anesthetics inhibit the norepinephrine uptake transporter, we hypothesized that this variable efficacy results from the local inhibiting the uptake of guanethidine. In this study, we tested this hypothesis by using a sympathetically innervated mouse vas deferens preparation. Organ bath-mounted mouse vasa deferentia were electrically stimulated in the absence and presence of guanethidine, prilocaine, procaine, and cocaine in various combinations. Prilocaine (1 mM) induced an immediate inhibition of twitch response (maximum 100% after 2 min) that fully reversed after washing. Guanethidine (3 microM) also inhibited twitching by 95% +/- 3% in 15 min, but this effect was only partially reversed after 1 h of washing (33% +/- 12% of control). When prilocaine and guanethidine were added in combination, a reversal of 80% +/- 13% (at 1 h) was observed. Procaine (300 micro M) produced a transient increase (152% +/- 14%) in response. When co-incubated with guanethidine (3 microM), the twitch was reduced to 24% +/- 4% of control and was reversed to 77% +/- 7% after 1 h. Cocaine (30 microM) inhibited the twitch response to 53% +/- 8%, which was fully reversed by 1 h of washing. When co-incubated with guanethidine, the response was reduced to 39% +/- 6% of control and was reversed to 86% +/- 10% after 1 h. In all cases, the reversal produced by the combination was significantly more intense (P < 0.05) than that produced by guanethidine alone. Local anesthetics reduce the sympatholytic actions of guanethidine, and this may explain the variable efficacy of guanethidine in the treatment of complex regional pain syndrome. IMPLICATIONS: In this study, with a sympathetically innervated vas deferens preparation, local anesthetics reduced the efficacy of the sympatholytic guanethidine, questioning its co-administration in the pain clinic.

Adrenergic Agents↗
PubMed1982

Immunosuppressive agents prevent guanethidine-induced destruction of rat sympathetic neurons.

Chronic administration of guanethidine to rats causes destruction of peripheral sympathetic neurons. Neuronal destruction, characterized morphologically by small cell infiltration and the reduction in the number of neurons within sympathetic ganglia, and biochemically by a marked reduction in tyrosine hydroxylase activity, occurred reproducibly by day 7 of treatment following 5 daily injections of 50 mg/kg guanethidine sulfate. Several observations in the literature suggested that guanethidine-induced destruction may occur by an immunologically mediated mechanism. Experiments were therefore designed to test the effects of immunosuppressive agents on guanethidine sympathectomy. A single exposure to either gamma-irradiation or cyclophosphamide, administered 8 h prior to the initiation of guanethidine treatment, protected against guanethidine-induced destruction in a dose-related manner and was virtually complete with either 900 rads of irradiation or with 100 or 150 mg/kg of cyclophosphamide. Cyclophosphamide afforded complete protection only if administered immediately prior to guanethidine treatment suggesting that it was acting during the proliferative phase of an immune response rather than non-specifically. Pretreatment with either irradiation or cyclophosphamide had no effect on the sympathectomy produced by treatment with either 6-hydroxydopamine or antibodies to nerve growth factor, nor did it prevent the accumulation of guanethidine within the sympathetic ganglia. Concurrent treatment with either azathioprine or dexamethazone also provided partial protection against guanethidine sympathectomy. These results strongly suggest that the destruction of sympathetic neurons induced by guanethidine occurs by an immunologically mediated mechanism.

Animals↗
PubMed1999

Dissociation of inhibitory effects of guanethidine on adrenergic and on purinergic transmission in isolated canine splenic artery.

The aim of this study was both to investigate the effects of progressive inhibition of adrenergic neurons by increasing concentrations of guanethidine (0.1-10 microM) on the double-peaked vasoconstrictor responses to electrical periarterial nerve stimulation in the isolated and perfused canine splenic artery, and to clarify whether release of noradrenaline is presynaptically separate from release of adenosine 5'-triphosphate (ATP). Double-peaked vasoconstrictions (biphases of vasoconstrictions) were consistently observed under the conditions of 30-s trains of pulses at 1-10 Hz frequencies. Guanethidine, at a lower concentration (0.1 microM) did not modify the first (1st) phase vasoconstriction at low frequencies (1-2 Hz), but markedly inhibited the second (2nd) responses. On the other hand, it slightly but significantly inhibited the double-peaked vasoconstrictor responses at high frequencies (6-10 Hz). Furthermore, a 10-fold increase of concentration of guanethidine (1 microM) almost completely inhibited the 2nd phase responses at any frequencies used but did not completely inhibit the 1st phase response. A further increased concentration of guanethidine (10 microM) failed to enhance the 1 microM guanethidine-induced inhibition. The 1 microM guanethidine-resistant 1st phase responses at any frequencies used (1-10 Hz) were sensitive to tetrodotoxin (30 nM). Treatment with 0.1 microM prazosin did not modify the 1st phase response at any frequencies used in the 1 microM guanethidine-treated preparation. The responses remaining after 1 microM guanethidine and 0.1 microM prazosin were completely suppressed by a subsequent application of 1 microM alpha,beta-methylene ATP at any frequencies used. The results indicated that guanethidine, an adrenergic neuron blocker, may exert a dominant inhibitory effect on adrenergic rather than on purinergic components of sympathetic nerve co-transmission, indicating that guanethidine-sensitive mechanisms may mainly contribute to determine noradrenaline secretion from neurosecretory vesicles rather than ATP secretion.

Adenosine Triphosphate↗
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↗