Action Of Reserpine Research Articles

Monoamine oxidase inhibiting properties of AB-15—Comparison with tranylcypromine, nialamide and pargyline

AB-15 ∗ is a potent inhibitor of MAO both in vitro and in vivo. Single oral application produces long lasting MAO inhibition. AB-15 reverses the action of reserpine and potentiates the 5-HTP induced rise in rectal temperature in mice while having a slight effect on the blood pressure and heart rate responses to tyramine in cats. The in vitro studies on the deamination of different amines, indicate that its inhibiting effect is selective, and dependes markedly on the substrate used.

Tissue catecholamines, blood glucose and plasma free fatty acids after combined treatment with reserpine and diuretics

The combined action of reserpine with either hydrochlorothiazide, furosemide or ethacrynic acid on the tissue catecholamines, blood glucose and plasma free fatty acids (FFA) was studied in rats. The animals were treated orally for one week with either hydrochlorothiazide, furosemide or ethacrynic acid, or for four weeks with hydrochlorothiazide and reserpine. A single reserpine injection was given 16 hr before killing. The heart noradrenaline content was increased after hydrochlorothiazide treatment. Hydrochlorothiazide antagonized the reserpine-induced noradrenaline depletion in the heart. Hydrochlorothiazide did not modify the kidney or brain noradrenaline contents nor the effect of reserpine on these. Furosemide had no influence on the catecholamines nor on the depleting effect of reserpine. Ethacrynic acid tended to decrease heart noradrenaline without altering the reserpine effect. Suprarenal adrenaline was rather resistant to the various drugs. Blood glucose level was lowered by ethacrynic acid and by combined hydrochlorothiazide-reserpine treatment. Plasma FFA level was increased in animals treated with hydrochlorothiazide and a single reserpine dose but decreased when these drugs were combined for four weeks. Reserpine Tissue catecholamines Diuretics Blood glucose Plasma FFA

Modification by metaraminol of reserpine action on noradrenaline stores in the rat heart

Metaraminol pretreatment lessens noradrenaline storage impairment by reserpine in the rat heart as shown by analyses of catecholamine organ concentrations 24 hr after reserpine administration.

Increased tyrosine hydroxylase activity after drug-induced alteration of sympathetic transmission.

AFTER the destruction of sympathetic nerve endings by 6-hydroxydopamine1,2, there is a compensatory increase in the catecholamine synthesis and tyrosine hydroxylase activity in the adrenal gland3. We have examined the actions of reserpine and phenoxybenzamine on adrenal tyrosine hydroxylase activity. These drugs, like 6-hydroxydopamine2, interfere with postganglionic sympathetic transmission, but by different mechanisms4–6. We also studied the alterations of this enzyme in an embryologically related tissue, the superior cervical sympathetic ganglion. Reserpine and phenoxybenzamine increased the activity of adrenal tyrosine hydroxylase, and reserpine also increased the activity of tyrosine hydroxylase in the superior cervical ganglion. This increase in enzyme activity was prevented by interruption of nerve impulses by decentralization.

Action of reserpine on antibody formation in hypophysectomized animals

Action of reserpine on antibody formation in hypophysectomized animals

Studies on the cardiotoxicity of ouabain.

Pretreatment with reserpine in a catecholamine-depleting dosage schedule greatly increased the arrhythmic and lethal dose of ouabain in cats. Pretreatment with reserpine immediately before the administration of ouabain also increased these doses significantly but the effect was less marked than that produced by 24-h pretreatment. Tetrabenazine provided protection comparable to that of reserpine when the latter was given immediately before ouabain. This finding suggests that the protective action of reserpine may be partially of central origin. The initial effect of bretylium was to reduce the toxic dose, but this was not the case if pronethalol was also administered. Pronethalol alone significantly increased tolerance to ouabain. Adrenaline in doses that did not induce arrhythmias markedly reduced the toxic dose of ouabain. Acetylcholine and eserine both increased the toxic dose, and the effect was atropine-resistant. Atropine itself did not exert a significant effect. Compound P-286 had no effect on the arrhythmic dose of ouabain, but it did increase the lethal dose. Halothane anesthesia did not markedly alter the arrhythmic dose but definitely delayed cardiac arrest. Procaine infiltration of the superior atriocaval junction provided significant protection. The most marked protection, however, was seen with hypothermia. Although numerous agents were found capable of markedly altering the mean amount of ouabain required to evoke ectopic rhythm, very few significantly altered the additional amount required to cause death, once sinus dominance was lost.

Les substances neuroleptiques et le comportement des insectes—VI. Influence de la reserpine sur le poids corporel de tribolium confusum duval

1. 1. The action of reserpine on Tribolium confusum Duval resulted in a great reduction of the animal's activity. 2. 2. The more or less sleepy beetles showed a decrease in their body weight. 3. 3. The insects become resistant when reared continuously on a medium containing the drug. 4. 4. When given a normal diet, they rapidly recovered their activity and body weight.

Differences in the duration of reserpine action in the rat depending on the measure employed.

The effects of reserpine were determined on eleven measures of drug action at 2, 26, and 50 hr following an acute injection. All measures were almost equally affected at 2 hr after injection and estimates of ED-50 from the log dose-effect curves ranged from 1·20 to 2·12 mg/kg. There were large differences, however, between the various indices in the time required for recovery from reserpine action. Five separate patterns of recovery would be distinguished. (1) Complete recovery within 26 hr; tremor and conditioned escape. (2) Partial recovery at 26 hr and complete recovery by 50 hr; muscle tone and hunched posture. (3) Little or no recovery at 26 hr but complete recovery by 50 hr; ptosis, exploratory behavior and lever pressing on variable interval schedules. (4) No recovery at 26 hr and only partial recovery by 50 hr; spontaneous locomotor activity and lever pressing on a continuous reinforcement schedule. (5) No recovery at 26 or 50 hr; the conditioned avoidance response. These differences in the duration of reserpine action are discussed with respect to differences in duration of neurochemical effects of the drug on monoamine in the brain.

Hepatotoxic effect of carbon tetrachloride during pregnancy

The hepatotoxic effect of CCl4 and the protective action of reserpine against the hepatotoxicity produced by this polyhalogen were studied in pregnant and nonpregnant animals. The pregnant animals were less susceptible to the hepatoxic effect of CCl4 and reserpine offered protection against CCl4 induced hepatotoxicity in both pregnant and nonpregnant animals.

The action of reserpine on noradrenaline biosynthesis in sympathetic nerve tissue

In postganglionic sympathetic nerve tissue, reserpine produced a marked inhibitory effect on the synthesis of noradrenaline from tyrosine. This block in synthesis was localized at the dopamine-β-hydroxylase step. In contrast to similar studies in nerve homogenates, dopamine was not observed to accumulate in the intact nerves exposed to reserpine except when monoamine oxidase (MAO) was inhibited by pargyline. However, a larger increase in the acid metabolites of dopamine (notably, dihydroxyphenylacetic acid) was found in the nerves and medium after reserpine treatment. This indicates that in nerve tissue MAO plays an important role in the degradation of any free dopamine which cannot be protected by being taken up into the granular vesicles and subsequently converted to noradrenaline. Inhibition with an MAO inhibitor partially reversed the inhibitory action of reserpine on noradrenaline biosynthesis. These studies indicate that in intact postganglionic sympathetic nerves, reserpine inhibits the synthesis of noradrenaline by inhibiting the uptake of the precursor dopamine into the granular vesicles which contain the enzyme necessary for its ultimate conversion to noradrenaline.

Action of Reserpine on Mouse Vas Deferens.

Australian Journal of Experimental Biology and Medical ScienceVolume 46, Issue 4 p. P-30-P-30 Original Article Action of Reserpine on Mouse Vas Deferens. Anna JC Ostberg, Anna JC Ostberg Department of Physiology, Monash University, Clayton, Vic. 3168Search for more papers by this authorMollie E Holman, Mollie E Holman Department of Physiology, Monash University, Clayton, Vic. 3168Search for more papers by this author Anna JC Ostberg, Anna JC Ostberg Department of Physiology, Monash University, Clayton, Vic. 3168Search for more papers by this authorMollie E Holman, Mollie E Holman Department of Physiology, Monash University, Clayton, Vic. 3168Search for more papers by this author First published: 01 August 1968 https://doi.org/10.1038/icb.1968.118AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume46, Issue4August 1968Pages P-30-P-30 Journal of the Australian and New Zealand Society for Immunology RelatedInformation

Temperature effects of reserpine injected into the cerebral ventricles of rabbits and cats.

1. In unanaesthetized rabbits and cats reserpine was injected through a chronically implanted cannula in the left lateral cerebral ventricle, and rectal temperature was recorded.2. In rabbits the reserpine (0.5-0.6 mg) caused a rise in temperature, frequent defaecation and sedation. On repeating the intraventricular injections at 24 hr intervals the rise in temperature was not obtained with the second or third injection, but defaecation and sedation still occurred. When the hyperthermic response to intraventricular reserpine had disappeared the anterior hypothalamus still responded to intraventricular noradrenaline which produced a rise in temperature.3. In cats the reserpine (0.5-0.75 mg) caused a biphasic change in temperature, i.e. an initial fall followed by a rise, frequent defaecation, and catalepsy. On repeating the intraventricular injections at 24 hr intervals the initial hypothermic phase of the temperature response was not obtained with the second or third injection, but the late rise, defaecation and catalepsy were still produced. When the hypothermic phase had disappeared the hypothalamus still responded to intraventricular noradrenaline or adrenaline which produced a fall, and to intraventricular 5-hydroxytryptamine (5-HT) which produced a rise in temperature.4. It is concluded that the rise in temperature in rabbits and the initial fall produced in cats is not due to a direct action of reserpine on the cells of the anterior hypothalamus but to noradrenaline released from adrenergic fibres ending at these cells. When these fibres are depleted of their noradrenaline by one or two injections of reserpine, these effects are not obtained because noradrenaline is no longer available to be released in sufficient amounts to raise temperature in rabbits and to lower it in cats.

Mechanisms of action of reserpine on gastric secretion of acid.

Mechanisms of action of reserpine on gastric secretion of acid.

Effect of 5-hydroxytryptamine and related compounds on the isolated heart ofPila globosa (Gastropoda: Mollusca)

5-hydroxytryptamine produces an increase in the amplitude and frequency of the heart-beat ofPila. The threshold for the activity of 5-hydroxytryptamine is 10−8 gm./ml. However, this dose is not constant. In some cases it is 10−6 gm./ml. and in still other cases doses even upto 10−4 gm./ml. are ineffective. The action of 5-HT is not blocked by LSD. However, LSD 10−5 gm./ml. produces a positive inotropic and a very slight positive chronotropic response. The bromine derivative of LSD sometimes causes a rise in the threshold of 5-HT. Reserpine produces a positive inotropic and a negative chronotropic effect. The threshold dose for Reserpine is 10−5 gm./ml. The action of Reserpine is of long duration and both increase in amplitude and decrease in frequency go on for a long time in a progressive manner. The action of 5-HT and related compounds on the heart ofPila has been discussed in relation to that in other molluscs.

The depletion and recovery of noradrenaline in the brain and some sympathetically innervated mammalian tissues after tetrabenazine.

Abstract The depleting effect of tetrabenazine on the monoamine levels appears generally to be less in peripheral tissues than in the central nervous system. The noradrenaline levels in brain and some sympathetically innervated tissues such as heart, submandibular glands, and skeletal muscle were examined in the rat after administration of the drug. The levels of 5-hydroxytryptamine, dopamine and noradrenaline were also estimated in the rabbit brain after tetrabenazine and compared with the levels in the rabbit heart. In both the brain and peripheral tissues the monoamine levels were strongly reduced 4 hr after tetrabenazine and increased thereafter, reaching normal levels after about 36 to 48 hr. The site of action of tetrabenazine is briefly discussed and compared to the site of action of reserpine.

Some pharmacological and biochemical properties of γ-morpholino-butyrophenone (NSD 2023), a new monoamine oxidase inhibitor

Some pharmacological and biochemical properties of γ-morpholino-butyrophenone (NSD 2023) are described. NSD 2023 has a weak sedative effect of 30–60 min duration, and a more pronounced anticonvulsant effect of similar duration, when the substance is administered subcutaneously. In tests for reserpine antagonism (reversal of reserpine induced hypthermia and ptosis), and monoamine oxidase (MAO) inhibition in vivo, the substance showed a pronounced effect of at least 4 hr duration. NSD 2023 inhibits mouse brain MAO maximally within 5 min after oral administration. The time required for the reappearance of 50 per cent of inhibited MAO is dose dependent and varies from about 5–17 hr. The maximum inhibition obtainable in vivo is about 80 per cent, and the oral dose required to produce 50 per cent of maximum inhibition is about 1.4 mg/kg. In vitro, maximum inhibition is about 55 per cent, and the concentration of NSD 2023 required to produce half-maximum inhibition is about 25 gmg/ml. Pretreatment of mice with SKF 525A has no apparent effect on the subsequent inhibition of brain MAO by NSD 2023 in vivo. Pretreatment of mice with NSD 2023 protects brain MAO against inhibition by phenelzine, pargyline, tranylcypromine, and iproniazid. Similarly, pretreatment with harmaline protects against inhibition by NSD 2023. MAO inhibition by NSD 2023 is only slightly reversed by repeated washes of the mitochondria. A single oral administration of NSD 2023 (50 mg/kg) increases the serotonin content of rat brain by about 50 per cent, but has no significant effect on the concentration of noradrenaline. Pretreatment of rats with NSD 2023 antagonizes the amine depleting action of reserpine. In mice, MAO in brain and kidney is inhibited more than MAO in liver. It is suggested that the antireserpine and anticonvulsant effects of NSD 2023 are not dependent on MAO inhibition as measured using tryptamine or kynuramine as substrate. It is also suggested that the incomplete inhibition of MAO by NSD 2023 reflects the existence of two or more forms of the enzyme.

The antagonism by thymoleptics of the reserpine-induced expansion of melanophores in the pencil fish

The pencil fish ( Nannostomus beckfordi anomalus) has been shown to be unsually sensitive to the melanophore expanding action of reserpine and several drugs have been tested for their ability to antagonise or modify this action of reserpine. Thymoleptic drugs were most active in antagonising the reserpine-induced colour change, and the results show that this effect may provide the basis for an experimental method of distinguishing thymoleptic drugs from neuroleptic drugs.

Promotion of 4-hydroxy-3-methoxyphenylglycol formation in man by reserpine.

THE ability of reserpine to bring about the depletion of biologically active amines in mammalian tissues1 is well known. This alkaloid also has several other biochemical effects which have recently been reviewed2, and we report a new and potentially important action of reserpine on catecholamine metabolism which was revealed during the course of another experiment3.

A Comparison of the Subcellular Sites of Action of Reserpine and Benzquinamide

P. Lundborg and Stitzel, R. E. A comparison of the subcellular sites of action of reserpine and benzquinamide. Acta physiol. scand. 1968. 72. 53–61. Both reserpinc and benzquinamide were capable of impairing the in uitro uptake of C14-adrenaline by bovine and rabbit adreno-medullary granules. however, they differed markedly in their relative potency. The in vivo studies using mice and the in vivo - in vitro studies employing rabbits indicated that the time course of granular blockade after reserpine and benzquinamide injections also differed. Benzquinamide was shorter-acting and less potent than was reserpine. Subcellular distribution studies indicated that while both drugs could impair the in vivo uptake of 3H-α-methyl noradrenaline, only reserpine administration resulted in both an increase in the amount of 3H-α-methyl noradrenaline found in the supernatant fraction and an increase in the amount of 3H-α-methyl normetanephrine recovered from the whole heart. It is concluded that while reserpine and benzquinamide have many qualitatively similar effects on amine uptake and depletion, differences in their actions on the subcellular level can be uncovered.

The antagonism between reserpine and some antiparkinson drugs in electroseizure.

The effects of amphetamine, metamphetamine, propylhexedrine, biperiden and atropine were studied in experiments on electroseizure threshold in rats. In high doses these drugs lowered the threshold of electroseizures and antagonized the threshold lowering produced by reserpine, with the exception of atropine, which enhanced the action of reserpine. Low doses of the drugs and combinations of low doses of metamphetamine, propylhexedrine and biperiden did not influence electroseizure threshold, but inhibited the action of reserpine. The effect of phenytoin on the threshold lowered by reserpine was enhanced by low doses of metamphetamine, propylhexedrine and biperiden. Tetrabenazine caused threshold lowering which was antagonized by metamphetamine, propylhexedrine, biperiden and atropine. Pretreatment with α-methyl-p-tyrosine, but not with diethyldithiocarbaminate abolished the effect of high doses of metamphetamine or propylhexedrine on the electroseizure threshold. Inhibition of the formation of DOPA or noradrenaline did not influence the action of reserpine or the antagonism between reserpine and the drugs of the amphetamine group. After a repeated injection of metamphetamine tachyphylaxis developed.