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PubMed1979

Incorporation of [U-14 C]glucose into metabolites of brain, liver and blood of rats pretreated with reserpine or phenothiazines.

Parkinsonism was induced in rats by using phenothiazines (Butyrylperazin and Thioproperazin). (P-group), or reserpine, (R-group). [U-14 C)D-glucose was administered when the symptoms of Parkinsonism had become fully developed. Concentrations and radioactivities of different metabolites were studied in brain, liver and blood serum. 1. Both types of treatments resulted in a decrease in the synthesis of amino acids from [14C]glucose in the brain. The concentrations of amino acids and the glycogen remained uneffected. Phenothiazines enhanced the conversion of lipids, while reserpine increased their concentration. 2. Reduced de novo synthesis of amino acids was recorded in the liver. Phenothiazines resulted in the storage of glycogen and lipids; reserpine resulted in the storage of lipids and enhanced the conversion of glycogen. 3. Both treatments caused a fall in the amino acid concentration of the blood serum. A rise in the specific radioactivity of blood amino acids was observed in the P-group, while a decrease in specific radioactivity was observed in the R-group. A hyperglycemia was induced in the R-group with reduced specific radioactivity of glucose in both P-and R-groups. A reduction in lipid concentration of blood serum was achieved with an increased specific radioactivity in P-group and decreased radioactivity in R-group. 4. The changes in amino acids common to both treatments are also observed in human Parkinsonism.

Amino Acids↗
PubMed1995

Influence of daily subcutaneous administration of reserpine for 4 weeks or 9 weeks before mating on testis, sperm and male fertility in rats.

To determine the optimum period of drug treatment and assessment parameters to evaluate male fertility in rats, different methods of examination and periods of treatment before mating were investigated in Sprague-Dawley (Crj:CD) male rats treated with a testicular oxicity-inducing agent, reserpine. The rats were given reserpine subcutaneously at daily doses of 0.05, 0.1 and 0.2 mg/kg for 4 and 9 weeks (4-week test and 9-week test). Reproductive performance was tested and after mating, the testes, epididymides, prostate and pituitary weights were measured. Sperm analysis and histopathological examinations of the genital organs were also performed in the 4-week test case. After 4 weeks, prostate weight was decreased and the implantation rate showed a tendency for decrease. Histopathological examination of the testes revealed changes such as retention of step 19 spermatids in the seminiferous tubules of stages IX to XII, although sperm analysis showed no abnormal findings. In the 9-week test, testes and prostate weights were decreased along with the implantation rate was decreased. In conclusion, of the approaches used to evaluate the effects of reserpine on male fertility, histopathological examination and measurement of genital organ weights proved more sensitive than reproductive performance testing and sperm analysis. Regarding the optimum treatment period, 4 weeks was found to be sufficient for detection of histopathological and genital organ weight changes.

Animals↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 7). Effects of reserpine in 2- and 4-weeks studies.

To assess the efficacy of different period of treatment for evaluating male reproductive toxicity in rats, reserpine was subcutaneously administered on a daily basis to male Sprague-Dawley rats at dosages of 0.05, 0.1 or 0.2 mg/kg for 2 weeks or at dosages of 0.05 or 0.1 mg/kg for 4 weeks. At the end of the administration period the animals were sacrificed and sperm counts, organ weights and histopathological changes in the reproductive organs were examined. The sperm number in the caudal epididymis and genital organ weights were not affected by reserpine with either 2- or 4-weeks treatment. In the 4-weeks study, histopathological examination of the testes revealed retention of step 19 spermatids in the seminiferous tubules of stages IX to XII and decreased secretory content of the prostate in the 0.05 and 0.1 mg/kg groups. In the 2-weeks study, although no distinct histopathological changes were observed in the 0.05 mg/kg group, decreased secretory content of the prostate, apoptosis of spermatocytes in the seminiferous tubules of stage VII and cell debris of the epididymis were observed in the 0.1 and 0.2 mg/kg groups. These results suggested that 2-weeks treatment with reserpine is sufficient for detection of testicular toxicity, although higher dosage levels are appropriate than for 4-weeks treatment.

Animals↗
PubMed1993

Ultracytochemical study of ouabain-sensitive K(+)-dependent p-nitro-phenylphosphatase activity in stria vascularis of reserpinized guinea pigs.

In order to clarify the effect of reserpine on the Na(+)-K+ active transport in the stria vascularis we investigated the localization of ouabain-sensitive K(+)-dependent p-nitro-phenylphosphatase (K-NPPase) activity in the stria vascularis of reserpinized guinea pigs using the cerium-based method. The K-NPPase activity in marginal cells differed from cell to cell, and was almost completely absent in some cells. These results are consistent with the previous results and suggest that Na(+)-K+ active transport in the stria vascularis may be inhibited by reserpine administration.

4-Nitrophenylphosphatase↗
PubMedDate not supplied

Tracheal potential difference in the reserpine and isoproterenol rat models of cystic fibrosis.

Basic research into cystic fibrosis (CF) has been hampered by the lack of a suitable animal model. Reserpinized or isoproterenol-treated rats have been proposed as models because they exhibit certain morphological and physiological features characteristic of CF. Recent evidence suggests that abnormal epithelial transport of Na+ [corrected] and Cl- may underlie pathogenesis, defects that may contribute to the markedly more negative transepithelial electrical potential differences (PD) recorded in CF airways compared with controls. To test the models further, we measured tracheal PD in vivo in treated rats (reserpinized - 6.9 mV, SEM 0.7 mV, n = 7; isoproterenol-treated -10.2 mV, SEM 1.5 mV, n = 12) and found it to be no different from that of controls (-8.7 mV, SEM 0.6 mV, n = 25). The animals did, however, demonstrate a reduced gain in body weight as well as increased submaxillary gland weight, which reflected an increased mucus content in the acini. These observations suggest that although the reserpinized or isoproterenol-treated rat may be useful in the study of the pathogenesis of exocrine disturbances in disease, their use as models for the effect of the basic defect of CF in the airways may be limited.

Animals↗
PubMed1980

Effect of reserpine upon the haemodynamic course of recovery following experimental myocardial infarction.

Acute haemodynamic consequences of coronary artery ligation were evaluated in twenty-four anaesthetized open-chest dogs, nine of which were pretreated with reserpine. The following parameters were measured before, and at 15-min intervals following ligation for at least five hours : ECG, mean arterial blood pressure, aortic blood flow, left ventricular pressure, heart rate, peripheral resistance (P.R.), end-diastolic pressure, dP/dtmax, and "internal work" (I.W. = heart rate x dP/dtmax). It was found that aortic flow was similar in control and reserpine-pretreated dogs (753 +/- 43 vs. 744 +/- 57 ml/min respectively), even though heart rate, blood pressure and other parameters were significantly higher in the control animals. Furthermore, the controls could be divided into two groups : recoverers (R) and non-recoverers (N), on the basis of late stage haemodynamic differences. The ratio of PR/IW taken within one hour of ligation was significantly higher in the R group (496 +/- 69) and reserpine group (479 +/- 30) than in the N group (242 +/- 28), and could predict course of recovery in each dog studied. It is concluded that the presence of myocardial catecholamines may be deleterious to the ischemic heart when the PR or IW are disproportionately altered.

Animals↗
PubMed1975

Effect on reserpine on humoral immune responsiveness in young chickens.

The role of reserpine in modifying a primary humoral immune response was evaluated in three experiments with young chickens. It was found that chickens injected with reserpine prior to an intravenous antigenic challenge with sheep red blood cells exhibited an enhanced primary humoral immune response. The enhanced response occurred concomitant with an elevation in adrenal cortical activity as evidenced by the significant elevation of serum corticosterone in the reserpine-treated chickens. These data suggest that both the adrenal cortex and medulla may influence immune responsiveness in the chicken.

Animals↗
PubMed1998

[Determination of hydrophobic pharmaceutical: tablet of reserpine compound by capillary zone electrophoresis].

Tablet reserpine compound is a kind of hydrophobic pharmaceutical that can not be separated by CZE with salt-water system. We solved this problem by adding organic component into the buffer. Thus a satisfactory separation of reserpine and hydrochlorothiazide was achieved by using a 24% (V/V) acetonitrile in the buffer solution of 10 mmol/L phosphate with a pH 9.0. The capillary column of 50 microns i.d. and 50 cm total length with effective length(the distance from the inlet to the detector) of 35 cm was used during all analytical procedure. The factors which influenced resolution such as the pH, acetonitrile content and phosphate concentration have been investigated. The CZE separation conditions of reserpine and hydrochlorothiazide using the standard mixture solution, are also showed. In the quantitative analysis, the reproducibility of CZE determination is illustrated. The regression coefficients of calibration graphs and the detection limits are given. The results of the study of recovery and quantitative results of these components using external standard method are given.

Drug Compounding↗
PubMed1975

Simultaneous changes in pancreatic and gastric secretion induced by acute intravenous ethanol infusion. Effect of atropine and reserpine.

The simultaneous effects of acute i.v. ethanol administration (1.3 gm./kg.) on pancreatic and gastric acid secretion was studied on dogs provided with chronic pancreatic and gastric fistulas (Thomas cannula) and subjected to a continuous i.v. injection of GIH secretin (0.5 CU./kg./hr.) and gastrin (Eurorga hog gastrin I-II, 6 gamma/kg./hr.). Acute i.v. ethanol inhibits the pancreatic secretion of protein (concentration and output) and stimulates gastric acid secretion. Experiments were repeated: 1. Superimposing an atropine infusion (1.0 mg./hr.) on the continuous hormonal perfusion. 2. After reserpine administration for 48 hours (0.10 mg./kg./24 hr.) Atropine abolished the ethanol-mediated inhibition of pancreatic protein secretion but did not prevent the alcohol-mediated gastric acid stimulation. Reserpine did not change the ethanol-mediated pancreatic inhibition. It is assumed that in nonalcoholic dogs, i.v. ethanol inhibits pancreatic secretion by an intermediate nervous mechanism and enhances gastric acid secretion by acting directly on the oxyntic cells. Reserpine induces a high plateau level of HCl secretion which obscures the ethanol-mediated excitatory influences on the oxyntic cells.

Animals↗
PubMed2002

[Study on the activities of fluoroquinolones against Staphylococcus aureus and the effect of reserpine on these activities].

OBJECTIVE: To investigate the activities of fluoroquinolones and the effects of reserpine on the activities of fluoroquinolones against S. aureus. METHODS: The minimal inhibitory concentration (MICs) and the effects of reserpine on MICs of fluoroquinolones against S. Aureus were determined using standard agar dilution method. RESULTS: Cross resistance to fluoroquinolones was found existing in S. aureus, but there was no remarkable multidrug resistance. The MICs of fluoroquinolones against many of S. aureus could be decreased by reserpine; Obvious decrease in MICs of fluoroquinolones against SA2-16 was observed; The decreasing percentage of MICs of fluoroquinolones against resistant strains was shown not significantly higher than that of sensitive strains. The decreasing percentage of MICs of hydrophilic fluoroquinolones against the strains studied was significantly higher than that of hydrophobic fluoroquinolones. CONCLUSIONS: Cross resistance to fluoroquinolones has been found existing in S. aureus, whereas multidrug resistance is not seen in existence. The efflux of fluoroquinolones is normal in S. aureus; the amount of fluoroquinolones effluxed is related with the resistance of fluoroquinolones in S. aureus.

Anti-Infective Agents↗
PubMedDate not supplied

Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats.

The aim of the present study was to find out whether a blockade of adenosine A2A receptors by the selective antagonist, SCH 58261, potentiates the attenuating effect of L-DOPA, the well-known antiparkinsonian drug, on parkinsonian-like muscle rigidity in rats. Muscle tone was examined using a combined mechano- and electromyographic method, which simultaneously measured muscle resistance of a rat hindfoot to passive extension and flexion in the ankle joint and the electromyographic (EMG) activity of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was produced by reserpine (5 mg/kg ip) injected in combination with alpha-methyl-p-tyrosine (alpha-MT, 250 mg/kg ip). L-DOPA (25 mg/kg ip) or SCH 58261 (0.1 mg/kg ip) administered separately, slightly influenced the reserpine + alpha-MT-induced muscle rigidity. However, only ankle joint extension was affected significantly while the effect on flexion of the rat hindfoot was not significant. Neither L-DOPA nor SCH 58261 given separately modified the reserpine-enhanced tonic or reflex EMG activities in both muscles examined. However, when L-DOPA (25 mg/kg) was given together with SCH 58261 (0.1 mg/kg), a clear synergistic effect was seen on both examined movements and muscles. The present results show that the blockade of adenosine A2A receptors potentiates the antiparkinsonian effect of L-DOPA. Since such an effect was seen in different animal models of Parkinson's disease (PD), it seems that co-administration of SCH 58261 may allow for the lowering of the doses of L-DOPA in clinical practice, which indicates a potential therapeutic value of this compound in the treatment of PD.

Adenosine A2 Receptor Antagonists↗
PubMed1976

Increased prolactin levels during reserpine treatment of hypertensive patients.

Serum prolactin levels are significantly greater among hypertensive patients receiving reserpine as compared to levels six weeks after discontinuing the treatment (P less than .005). This association between regular, long-term reserpine use and greater prolactin levels may be clinically significant, since an increased incidence of breast cancer has been reported among hypertensive patients receiving reserpine.

Androstenedione↗
PubMed1976

[Influence of reserpine on the nasal mucous membrane (author's transl)].

The influence of reserpine on the nasal mucous membrane in the various conditions of its autonomic denervation was investigated in the rabbits. Histochemical analysis of a acetylcholine esterase and quantitative measurements of acetylcholine were performed. The results point out that reserpine influence is found only on the vascular elements in the mucous membrane and not on the subepithelial glands. Analogically it was concluded that in some patients with arterial hypertension who were treated with reserpine, its side effect, nasal obstruction, was caused only by vasodilatation. In rhinitis vasomotorica, in the addition to the vasodilatation the abounding secretion of subepithelial mucous glands is present. The performed experiments also point out that resection of the vidian nerve in resistant cases of vasomotor rhinitis with aboundant secretion is reasonable.

Acetylcholinesterase↗
PubMed1976

"Direct" effect of reserpine on various preparations.

The action of reserpine added to the bathing solution has been studied in isolated organs, examining various kinds of receptor systems and biological preparations. The investigation has been comparatively carried out in normal and reserpine-pretreated animals. The most important effect of reserpine is the inhibition of the maximum response to noradrenalin in the rat vas deferens, and the inhibition of response to furtrethonium and histamine in the intestine of rat and guinea-pig, respectively. This affect appears to be independent of the release of catecholamines, and is therefore direct, aspecific and similar to the non-competitive effect of papaverine.

Animals↗
PubMed1992

Acetylcholine contents and muscarinic receptor levels in frontal cortex, corpus striatum, and hippocampus of reserpinized rats and mice.

The acetylcholine (ACh) levels in rat and mouse frontal cortex increased 155% and 124%, respectively, 24 h after ip reserpine 3 mg.kg-1. Striatal ACh contents, however, were diminished by 47% in rats and 80% in mice. ACh contents elevated 50% and scopolamine (Scop) depleted the ACh by 47% in mouse striatum 12 h following reserpine. Receptor binding assay showed that 24 h after reserpine the Bmax of [3H]quinuclidinyl benzilate ([3H]QNB) binding to muscarinic receptors increased in frontal cortex (by 33% in rats, by 30% in mice) and decreased in striatum (31% in rats, 26% in mice). In mouse hippocampus the ACh contents, Bmax, and affinity of muscarinic receptors lowered 63%, 19%, and 26%, respectively. But these changes were not seen in rat hippocampus.

Acetylcholine↗
PubMedDate not supplied

[Historical approach to reserpine discovery and its introduction in psychiatry].

Reserpine, an alkaloid of the Rauwolfia serpentina plant isolated during the middle of the 20th Century, represented a highly important clinical advance in the treatment of schizophrenia whose pharmacological tools were limited to chlorpromazine that was introduced in the clinical area two years before. Both agents would come into the history as the drugs that made possible the beginning of the psychopharmacological era. In the present article, a revision is made of the complicated process leading to the isolation and synthesis of reserpine, by the Swiss pharmaceutical company Ciba (Schlittler and Müller) and how its pharmacological properties (Bein) were discovered and studied, in the animals laboratory, mainly, the "tranquillizers". The introduction of this antipsychotic in psychiatry, which was initiated in 1954 (half a century ago), and the results obtained in the first clinical studies, as well as the role played by researchers such as Kline, Delay, Noce, Hollister, Altschule, etc. are then described. In addition, and from a historical perspective, the discovery of the adverse effects of this drug, especially those of extrapyramidal nature (dyskinesia and akathisia), are studied, concluding with the reasons that produced its rapid clinical decline, among which the genesis of depressive pictures (phenomenon presently questioned) may be emphasized. Finally, the conclusion reached was that, although the clinical relevance of reserpine was not as evident and long lasting as chlorpromazine, its initial contribution to the treatment of schizophrenic patients was of maximum importance.

Adrenergic Uptake Inhibitors↗
PubMed1999

[Study on the ingredients of reserpine by TLC-FT-SERS].

A new method for analysing the ingredients of reserpine by thin layer chromatography (TLC) and surface-enhanced Raman spectroscopy (SERS) is reported in this paper. The results show that the characteristic spectral bands of reserpine satuated at the thin layer with the amount of sample about 2 microg were obtained. The difference between SERS and solid spectra was found. An absorption model of reserpine and silver sol was proposed. This method can be used to analyse the chemical ingredients with high sensitivity.

Chromatography, Thin Layer↗
PubMedDate not supplied

Experimental research about the influence of pentazocine and reserpine on morphine addiction.

By means of a conveyer belt two types of conditioned reflexes were developed in rats, at two functional levels. When these had become stable, we observed the animals' behaviour during a morphine treatment, until they developed tolerance. Thereafter the treatment with morphine was suddenly discontinued, or morphine was replaced by pentazocine or reserpine. We found that morphine impaired both types of conditioned reflexes and that ni about two weeks drug tolerance appeared. When treatment was discontinued a syndrome of abstinence developed, which exclusively impaired the conditioned reflex of the second order. Pentazocine and reserpine prevent such manifestation of the abstinence syndrome. Moreover, reserpine suppresses the tolerance to morphine. Concerning these results we suppose that opioid receptors type mu are involved in behavioural trouble produced by morphine, while opioid receptors type k are involved in the abstinence syndrome. Certain adrenergic mechanisms operate both in the development of tolerance and in behavioural modifications caused by the syndrome of abstinence.

Animals↗