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PubMed1989

Mitoxantrone & adriamycin cytotoxicity enhanced by reserpine in human chronic myeloid leukaemia cells.

The effect of reserpine was studied alone and in combination with anticancer drugs on human chronic myeloid leukaemia (CML) cells. To study the effect of reserpine on anthracycline antibiotic adriamycin and anthracenedione mitoxantrone the extent of 3H-thymidine incorporation into the DNA was taken as the measure of cytotoxicity. The results indicate that reserpine enhances the cytotoxicity of mitoxantrone and adriamycin in mildly toxic concentrations (1 and 10 micrograms respectively), in CML cells. The mechanism of enhancement in drug sensitivity by reserpine in CML cells is due to enhanced intracellular accumulation of drug.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Determination of reserpine and rescinnamine in Rauwolfia serpentina preparations by liquid chromatography with fluorescence detection.

A method is presented for the determination of reserpine and rescinnamine in Rauwolfia serpentina powder or tablets by liquid chromatography (LC) with fluorescence detection. The sample is dispersed in CH3OH, 0.5N H2SO4 is added, and the mixture is extracted with five 30 mL portions of CHCl3. The extracts are separated from interfering materials on a Celite-0.1N NaOH column, and the eluates are collected in 50 mL CH3OH. After complete removal of the CHCl3, reserpine and rescinnamine are determined by liquid chromatography on a normal phase column with CH3OH as the mobile phase. Because reserpine and rescinnamine produce a single peak, chromatograms are obtained at different wavelengths. Reserpine is determined at an excitation wavelength of 280 nm and an emission wavelength of 360 nm. Rescinnamine is determined at an excitation wavelength of 330 nm and an emission wavelength of 435 nm. Recovery studies were conducted at 2 different levels to simulate 100 and 50 mg Rauwolfia serpentina tablets. Samples of Rauwolfia serpentina powders and tablets were also examined, and the results were compared with those obtained by the current AOAC official method. The proposed method is applicable to the analysis of ground composites and individual tablets.

Chromatography, Liquid↗
PubMed1986

Reversal by L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a L-norepinephrine precursor of reserpine- or tetrabenazine-induced hypothermia.

The effects of L-threo-DOPS on the hypothermia and the decrease of brain norepinephrine (NE) concentration in the mouse pretreated with reserpine or tetrabenazine were studied. Reserpine (5 mg/kg, i.p.) or tetrabenazine (40 mg/kg, i.p.) produced a significant decrease in body temperature. The i.p. injection of L-threo-DOPS (100, 200 and 400 mg/kg) reversed these hypothermia in a dose-dependent manner. These hypothermia were also antagonized by the i.c. injection of NE (5 micrograms/mouse). Both reserpine and tetrabenazine markedly decreased the brain content of NE, and L-threo-DOPS (400 mg/kg, i.p.) recovered it. These results suggested that L-threo-DOPS would reverse the reserpine- or tetrabenazine-induced hypothermia at least in part by the formation of NE in the central nervous system.

Animals↗
PubMed1979

[Studies on the relationship between the endotoxin induced fever and the antipyretic effect of reserpine in rabbits (author's transl)].

It has been well documented that fever could be mediated with endogenous pyrogen released from reticuloendothelial system(RES) by administration of bacterial endotoxin(LPS) intravenously to rabbits. On the contrary, reserpine which has various pharmacological activities by depleting catecholamines decreases the normal body temperature as well as endotoxin induced fever. In this paper, we focussed our attention on the effect of reserpine on the production of endogenous pyrogen with relation to the antipyretic effect in endotoxin fever and obtained the following results: Endogenous pyrogen could be detected by intravenous administration of LPS(0.5 micrograms/kg) during the fever. However, endogenous pyrogen was undetectable with intracisternal administration of LPS(0.01 microgram/body) which provoked long-lasting fever. Reserpine (1 mg/kg, i.v.) decreased both body temperature induced by intracisternal administration of LPS(0.01 microgram/body) or intravenous administration of LPS(0.5 microgram/kg), however the degree was more extensive in cases of LPS-induced fever. Pretreatment of rabbits with reserpine (1 mg/kg, i.v.) suppressed the fever induced by an intravenous administration of LPS(0.5 microgram/kg), but did not suppress the release of endogenous pyrogen. These data suggest that endogenous pyrogen may not be an important factor in the pathogenesis of endotoxin fever.

Animals↗
PubMed1987

Norepinephrine depletion and sensitivity changes in rat heart induced by pretreatment with reserpine.

Depletion of norepinephrine, sensitivity to isoproterenol and sensitivity to tyramine in rat atria were investigated after various doses and schedules of pretreatment of rats with reserpine. Virtually complete depletion of norepinephrine occurred in both right and left atria and ventricles after doses of 1.0 mg/kg/day of reserpine for one or more days of pretreatment. A smaller dose, 0.3 mg/kg/day, produced lesser depletion, and a larger dose, 2.5 mg/kg/day, caused severe central nervous system depression and high mortality. Chronic treatment (5 days or longer) with the 1.0-mg/kg/day dose produced supersensitivity of right atria to the chronotropic, but not inotropic, responses to isoproterenol. Chronic treatment with this dose for 7 days produced inotropic supersensitivity in left atria. Most of the schedules of pretreatment with reserpine depressed the maximum response to tyramine. However, the data indicate that the tyramine-releasable norepinephrine was not a consistent reflection of the total norepinephrine pool, even when depletion was very pronounced. The effects of depletion of cardiac stores of norepinephrine with reserpine in comparison with the effects of cardiac sympathectomy are discussed.

Animals↗
PubMed1987

Effects of reserpine treatment on the ultrastructure of rat parotid and submandibular gland.

The chronically reserpine-treated rat has been used as an animal model for the disease cystic fibrosis, a generalized exocrinopathy. Ultrastructural changes in the parotid and submandibular gland occurring during the seven-day treatment with reserpine were studied by transmission electron microscopy. In the parotid gland, marked changes were observed in the size and structure of the zymogen granules. In fasted control animals, most parotid acinar cells have granules with a virtually homogeneous, electron-dense appearance. During the first three days of treatment, most cells have enlarged, electron-translucent granules. After the third day, and most pronounced at day six and seven, many granules are irregularly electron-dense. In the submandibular gland, reserpine causes a gradual increase in the relative volume of the cell that is occupied by mucus. The ultrastructural changes are discussed in relation to metabolic and biochemical effects of reserpine treatment on salivary glands.

Animals↗
PubMed1986

[Opsoclonus-polymyoclonia syndrome suppressed with reserpine].

A 38-year-old man was admitted to Iwakuni National Hospital on July 6, 1978, with the complaints of difficulty seeing and walking. Two weeks before admission, he first experienced dizziness and it slowly progressed to uncontrollable tremor-like movements of the whole body. On admission, he was alert, oriented and afebrile. He had not experienced nausea, vomiting nor headache. He showed irregular horizontal oscillations of the eyes. Electronystagmographic study showed that this jerky eye movement appeared especially with changes of fixation of the eyes. It was also recorded during conjugate eye movement, and while he closed his eyes. He was ataxic, unable to walk, but no other abnormalities in cerebellar functions were observed. Spinal tap was performed and yielded watery clear cerebrospinal fluid containing 9/mm3 mononuclear cells. Clonazepam was given, 1.5 mg per day, for three days followed by doses of 3 mg per day. Improvement in walking was observed one week after starting the medication, when reserpine was started at a dose of 1 mg per day and increased to a dose of 1.5 mg per day in three days. One week after starting reserpine, opsoclonus improved markedly and he became able to read again. He was discharged home on September 3, 1978. Six months after admission, reserpine was decreased to 0.5 mg per day. Difficulty in reading developed within a month. Reserpine was given 1.0 mg per day and the doses was continuously given for next three months. One year after admission, he is back to his former occupation without medication. He complains of slight difficulty in reading for more than an hour, and in watching TV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Effects of reserpine and adrenal demedullation on brown adipose tissue thermogenesis induced by dl-phenylpropanolamine.

The contribution of catecholamine release to activation of brown adipose tissue (BAT) thermogenesis induced by dl-phenylpropanolamine (dl-PPA) was assessed in adult male rats. The rats underwent adrenal demedullation or not and were then treated (2X) with 5 mg/kg reserpine or 0.9% saline over a 24 hour period. Interscapular BAT (IBAT) and rectal temperatures were recorded for 10 minutes prior to and 30 minutes following treatment were induced by dl-PPA. Significant increases in IBAT temperature were induced by dl-PPA treatment in sham-operated and demedullated rats but but not in sham-operated or demedullated rats treated with reserpine. The action of reserpine on IBAT thermogenesis induced by PPA was not an artifact of reduced feeding associated with reserpine treatment as rats deprived of food for 24 hours exhibited normal thermogenesis to 10 mg/kg dl-PPA. These data document the role of non-adrenal catecholamines in IBAT thermogenesis induced by dl-PPA.

Adipose Tissue, Brown↗
PubMed1985

Exclusion bias and the false relationship of reserpine and breast cancer.

Although reserpine has an important role in treating patients with hypertension, its appeal was sharply reduced a decade ago when an alleged relationship to breast cancer was reported in case-control studies. Since the relationship was not confirmed in subsequent research and analyses, the original association is now regarded as erroneous. Since patients with cardiovascular disease were rejected as possible controls in the original reserpine-breast cancer case-control study, we suspected that the false association may have been produced by a phenomenon called exclusion bias. This bias can arise in case-control studies if patients with a particularly high (or low) rate of prior exposure to the alleged etiologic agent are excluded from the selection of either cases or controls, but not from both. To test that suspicion, we recapitulated the original study, in another medical setting. The cases were 257 women with breast cancer; and the controls were 257 hospitalized women matched according to date of admission, age, and race. The overall data showed no association between reserpine and breast cancer (odds ratio [OR] = 1.1), but when we excluded 101 women with cardiovascular disease from the control group, the OR rose to 2.5. The results suggest that exclusion bias played an important role in creating the false association between reserpine and breast cancer.

Aged↗
PubMed1977

[Direct effect of reserpine. II. Response of the rat vas deferens to calcium].

It has been shown that reserpine competitively antagonises the response of the isolated rat vas deferens to Ca2+. It has also been shown that reserpine does not modify uptake of Ca2+ from the external medium. On the basis of the results obtained and bearing in mind the uncoupling effect of reserpine on oxidative phosphorylation, it is suggested that reserpine owes its "direct" action to reduced availability of Ca2+ for contraction due to metabolic block.

Animals↗
PubMed1981

Effects of chronic reserpine administration on beta adrenergic receptors, adenylate cyclase and phosphodiesterase of the rat submandibular gland.

Chronic administration of reserpine to rats resulted in a doubling of the density of beta adrenergic receptors in submandibular gland membranes as determined by [3H]dihydroalprenolol binding. The affinity of the labelled drug for the receptor were not altered. There was a concomitant increase in the isoproterenol-stimulated cyclic AMP levels in slices of the gland when incubated in the absence of a phosphodiesterase inhibitor. However, this increase in cyclic AMP accumulation appears to be related to a decrease in phosphodiesterase activity rather than to the increase in the density of beta receptors, since glands from control and reserpinized animals accumulated equal amounts of cyclic AMP when incubated in the presence of a phosphodiesterase inhibitor. In addition, there was no difference between glands from controls and reserpine-treated rats in catecholamine-stimulated adenylate cyclase activity, but the Vmax of the phosphodiesterase was decreased 36% in glands from the treated animals. Similar results were obtained when control and surgically denervated glands were compared. The increase in beta adrenergic receptors appears to be the result of the depletion of norepinephrine due to reserpine administration, whereas the decreased phosphodiesterase activity may result from decreased cyclic AMP levels, secondary to the decrease in norepinephrine.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMedDate not supplied

Effect of intra-arterial reserpine in patients suffering from Raynaud's phenomenon.

Several papers have established the beneficial effect of Reserpine applied intra-arterially in patients suffering from Raynaud's phenomenon. In the present study this effect was investigated in 15 patients, some of whom had been submitted previously to sympathectomy, and in healthy controls. A solution of 1.25 mg Reserpine in 10 ml normal saline was injected in the course of one minute in the brachial artery. Blood pressure, pulse rate, bilateral finger venous occlusion plethysmography and fingertip temperature measurements were carried out for two hours following the injection. Later, venous occlusion plethysmographic and clinical controls were continued weekly, until the Reserpine effect had ceased. Normal subjects, patients suffering from Raynaud's phenomenon undergoing no surgical treatment and those submitted to preganglionic sympathectomy showed a conspicuous increase in digital blood flow, while in one patient, who had stellectomy the fingerflow remained unchanged. This effect remained chiefly located on the injected side. There were no blood pressure or pulse rate changes while in the lying position. Hypotension by passive orthostasis was observed two hours after the injection. The possible mechanism of Reserpine is discussed.

Adult↗
PubMed1984

Reserpine plus hydrochlorothiazide and sotalol plus hydrochlorothiazide in Black and Indian hypertensive patients.

Fifty patients (25 Blacks and 25 Indians) suffering from mild-to-moderate hypertension (supine diastolic blood pressure 100 - 105 mmHg) were studied in order to compare the antihypertensive effect of a combination of a beta-blocker (sotalol hydrochloride 160 mg/d) plus a thiazide derivative (hydrochlorothiazide 25 mg/d) ( Sotazide ; B-M) with that of a combination of reserpine 0,1 mg/d ( Serpasil ; Ciba) plus hydrochlorothiazide 25 mg/d ( Dichlotride ; Frosst MSD). The combination of reserpine plus hydrochlorothiazide was found to be as effective as that of sotalol plus hydrochlorothiazide in lowering the blood pressure in both the Black and the Indian patients. Two patients taking the combination containing reserpine developed side-effects, but this did not occur in any of those taking the combination containing sotalol. We feel that in developing countries, where the cost of therapy is important, reserpine in a dosage of less than 0,1 mg/d plus a thiazide derivative in low dosage is preferable to a beta-blocker plus a thiazide derivative in the treatment of hypertension.

Blood Pressure↗
PubMed1984

Effects of a gastric antisecretory-cytoprotectant 2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine-3-acetonitrile (Sch 28 080) on cysteamine, reserpine and stress ulcers in rats.

Prostaglandin E2 and carbenoxolone, putative cytoprotective agents, were tested in cysteamine, reserpine and stress ulcers in rats. In cysteamine-induced duodenal ulcer, PGE2 was inactive at 0.1 and 0.5 mg/kg p.o.; carbenoxolone at 100 mg/kg p.o. decreased the incidence but not the severity of the ulcer. PGE2 at 5.0 mg/kg p.o. and carbenoxolone at 300 mg/kg p.o. showed moderate effects, but the dosage also inhibited cysteamine-stimulated acid secretion. PGE2 (0.1 and 0.3 mg/kg p.o.) was inactive and carbenoxolone (100 and 300 mg/kg p.o.) further aggravated the gastric ulceration caused by reserpine or cold-restraint stress. In contrast, atropine (3 and 10 mg/kg p.o.) and cimetidine (30, 100 and 300 mg/kg p.o.) were active in all three ulcer models. But the results with cimetidine in stress ulcer were somewhat variable. 2-methyl-8-(phenylmethoxy) imidazo [1,2-a] pyridine-3-acetonitrile (Sch 28 080), a novel structure with both cytoprotective and antisecretory activity, was highly efficacious in cysteamine, reserpine and stress ulcers (1-30 mg/kg p.o.), which was presumably adequately accounted for by its potent antisecretory activity. It is concluded that cysteamine, reserpine and stress ulcers may not be appropriate models for testing the potential antiulcer effect of primarily cytoprotective compounds.

Animals↗
PubMed1983

Intra-arterial reserpine for Raynaud's syndrome. Systemic reactions without therapeutic benefit.

Twenty-four patients classified as having Raynaud's disease or Raynaud's phenomenon were given bilateral brachial artery injections of reserpine or saline in a double-blind fashion. In the six weeks following injection, there was no indication that reserpine produced clinical improvement or changed vasomotor reactivity in the treated patients. However, intra-arterial reserpine did produce systemic cardiovascular effects lasting up to six weeks. It is concluded that intra-arterial reserpine as used in this study is an ineffective treatment for Raynaud's disease or Raynaud's phenomenon and may have significant adverse effects.

Adult↗
PubMed1983

The value of the reserpine test in psychopharmacology.

Numerous tests have been proposed to search for a possible antidepressive action. Many of these tests are based on a reversal of different reserpine effects, an approach justified mainly by the use of most the classic or new antidepressants. Three effects of reserpine were examined in mice: hypothermia, ptosis and akinesia. All tests were performed with reserpine 2.5 mg/kg, and the drugs were injected 4 h after reserpine administration. In these three models, we studied the relatively specific effects of 21 drugs known for their influence on the metabolism or action of norepinephrine (noradrenaline), serotonin and dopamine. Our results suggest that hypothermia antagonism is only obtained with drugs stimulating beta-adrenergic receptors directly or indirectly, ptosis antagonism with those stimulating alpha-adrenergic or serotonergic receptors, and akinesia antagonism with those stimulating dopaminergic receptors.

Animals↗
PubMed1981

Enhancement of thrombin-induced degradation of phosphatidylcholine in reserpinized rabbit platelets.

When 1-(14)C-arachidonic acid-labeled, washed platelets from the reserpinized rabbits were exposed to thrombin, the decrease in radioactivity of phospholipids was significantly stimulated as compared with the control platelets. The increase in radioactivity of fatty acids and their oxygenated metabolites was also stimulated. TLC analysis revealed that the stimulation of the decrease in radioactivity of phospholipids was almost exclusively attributed to that of phosphatidylcholine (PC), and that thrombin induced a slight but significant increase in radioactivity of phosphatidylethanolamine (PE) in the reserpinized platelets. The results suggest that thrombin-induced degradation of PC is enhanced in the reserpinized platelets, and the overproduced fatty acids would be metabolized to the larger amount of oxygenated products which result in the activation of the platelets. Thrombin-induced mobilization of PC to PE in the reserpinized platelet phospholipids was also suggested.

Animals↗
PubMed1980

Influences of Mg++ and reserpine on calcium fluxes and sensitivity of the rat aorta.

Rat aorta became supersensitive and subsensitive to noradrenaline (NA), respectively, in Mg++-free and 3.6 mM Mg++ media reserpine treatment reduced the sensitivity in normal or high (3.6 mM) Mg++ media but had no effect in Mg++-free medium. Incubation of aortae in Mg++-free medium enchanced 45Ca++ uptake and efflux in rat aorta, whereas, it reduced 45Ca++ efflux without a change in 45Ca++ uptake by rabbit aorta. Reserpine pretreatment enhanced 45Ca++ efflux from rat aorta without a changed in 45Ca++ uptake in normal Mg++-free medium. Unlike in rat aorta, reserpine enhanced 45Ca++ uptake by and reduced efflux from rabbit aorta in Mg++-free medium but not in normal medium. These results suggest that the failure of reserpine to induce supersensitivity in rat aorta to NA may be due to poor capacity of the muscle to retain Ca++ and probably also due to an enhanced antagonism of Mg++ on Ca++ movements.

Animals↗