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[The action of reserpine in experimental rabies infection].

Experimental studies in laboratory animals showed reserpine in doses of 0.01-0.05 mg/kg body weight to inhibit the development of rabies infection in white mice and rabbits by 40.0-83.4% depending on the dose and mode of administration. The inhibiting properties of reserpine were demonstrated for both fixed and street rabies virus strains. The protective effect of the drug was manifested after parenteral and oral administration to the infected animals. The experimental data suggest that reserpine may be used as an antiviral drug for protective treatment of rabies in the incubation period.

Administration, Oral↗
PubMed1977

Potassium release from the rat submaxillary gland in vitro. III. Effects of pretreatment with reserpine.

The release of K+ from submaxillary gland slices of rats pretreated with reserpine was compared in vitro with that from control slices in paired experiments involving stimulation with catecholamines and with cholinergic secretagogues. The slices were incubated at 37 degrees C in enriched Krebs-Ringer bicarbonate medium gassed with a 95% O2-5% CO2 mixture, in the presence and in the absence of ouabain, Ca++, substrates and specific antagonists. The results indicate that: 1) slices from the treated animals had a similar extent of basal (unstimulated) net K+ release but a significantly higher extent of stimulated net K+ release than control slices; 2) in the presence of ouabain, slices from control and treated animals had similar extents of K+ efflux during basal and stimulated conditions; 3) removal of glucose from the medium resulted in an increased net K+ release from both types of slices, but removal of both glucose and the purines further increased net K+ release from control slices but not from those of treated animals; 4) blockade of receptors 2 minutes after stimulation resulted in a slower rate of K+ reuptake in the slices from treated animals when alpha receptors were blocked with phenolamine but not when cholinergic receptors were blocked with atropine; 5) removal of Ca++ from the medium inhibited the response to norepinephrine and to carbachol, but subsequent addition of Ca++ resulted in a higher extent of net K+ release form the slices of treated animals after norepinephrine, but not carbachol stimulation; 6) there was a 2.57-fold shift to the left and a 3.47-fold shift to the left in the dose-response curve to norepinephrine and carbachol, respectively, after pretreatment with reserpine. It is concluded that reserpine pretreatment: 1) alters the ability of the salivary cells to recover the extruded K+ and 2) induces supersensitivity to secretagogues which is most likely related to changes in the physiological state of the salivary cells.

Acetylcholine↗
PubMed1976

[Reserpine in the prevention of migraine and in the therapy of tension-vascular headache].

The results of many researches on migraine pathogenesis and our knowledge of the pharmacological action of reserpine led us to start using it in migraine prophylaxis ten years ago. For this purpose, standardized cycles of twenty administrations--heach dose being of 0.20 mg--were given intravenously; each cycle lasted a period of six to eight weeks. The positive data obtained on 300 patients suffering from severe migraine resulted statistically significant. Then, a double-blind clinical trial was carried out in Turin in agreement with a double-blind biochemical trial carried out in Copenhagen by Fog-Møller, Dalsgaard-Nielsen, Byrndum and Kemp Genefke. The results obtained have confirmed the efficacy of reserpine administered in appropriate doses and enabled the demonstration of its pharmacological mechanism. The results obtained also in "tension-vascular headache" with reserpine treatment were reviewed retrospectively and were highly significant.

Headache↗
PubMed1998

Influence of reserpine on iron absorption in rats.

The aim of our investigations was to define the influence of reserpine on iron absorption in rats. Iron absorption was determined in vivo at the 24th hour and in situ in a tied-off intestinal segment. Five-days treatment with reserpine (1 mg/kg b.wt) led to suppressed bone marrow erythropoiesis, manifested a considerable decrease in reticulocyte count and in a percentage of 59Fe-incorporation into newly formed erythrocytes. Increased plasma iron and decreased plasma ferritin levels were found. Iron absorption was found to be significantly increased, in spite of the suppressed erythropoiesis. The major conclusions of the experiments are, that reserpine interferes with the regulation of iron metabolism and erythropoiesis.

Animals↗
PubMed1988

Penile paralysis and paraphimosis associated with reserpine administration in a stallion.

Reserpine was administered to an 8-yr-old Thoroughbred stallion at a dosage of 5 mg subcutaneously (s.c.) every 2 wk for a 2-mo period to control unmanageable behavior. Reserpine produced a satisfactory calming effect that lasted for about 2 wk. After the last injection, the stallion developed penile paralysis and was unable to retract his penis, resulting in paraphimosis and attendant penile edema. The prolapsed penis was reduced and kept within the prepuce by placing a purse string suture in the preputial orifice. Phenylbutazone was given orally (1 gm) and the stallion was exercised for 20 to 30 min twice daily. This treatment was continued for 20 d with little improvement. The purse string retention suture cut through the skin 5 d after the stallion was discharged from the clinic. The penis was then supported against the abdominal wall and the stallion was exercised by hand for 30 min each day. The stallion was not used for breeding within 34 mo after the last injection of reserpine. A breeding soundness examination was performed approximately 3 yr after the initial injury. At this time the stallion's penis was noted to extend 5 to 8 cm from the prepuce when in a detumescent state. Although the stallion protruded his penis when exposed to a mare in estrus, a full rigid erection was never attained. Examination of the penis revealed partial engorgement of the corpus cavernosum penis and a 2.5-cm-wide dorsal semi-circumferential depression of the penile shaft approximately 10 to 12 cm proximal to the glans penis. The penile shaft and glans penis distal to this depression were cooler than the proximal portion of the penis. Semen collection was attempted, aided by manual insertion of the penis into the artificial vagina. When serving the artificial vagina, no "belling" of the glans penis was observed, although ejaculation occurred. Semen evaluation indicated normal spermatozoal motility and morphology parameters. The stallion was able to breed several mares with manual assistance to guide the penis into the vagina and one mare was diagnosed pregnant.

Journal Article↗
PubMed1994

Effect of a reserpine-like agent on the release and metabolism of [3H]NA in cell bodies and terminals.

1. The reserpine-like agent, Ro4-1284 (2-hydroxy-2ethyl-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro- 11b-[H] benzo (a)quinolizine) releases [3H]noradrenaline ([3H]NA) from prelabelled superior cervical ganglion (cell bodies) and nictitating membrane (nerve endings) of the cat. 2. The potency of Ro 4-1284 29.0 microM was higher in the cell bodies than in the nerve endings. 3. In both tissues, exposure to the reserpine-like agent Ro 4-1284 induced a selective increase in the spontaneous outflow of [3H]DOPEG, while the [3H]OMDA metabolites to the release induced by Ro 4-1284 was very small. 4. The desamination is the preferential way of the metabolic inactivation of the [3H]NA released by the reserpine-like agent in both parts of the noradrenergic neuron.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1999

Effects of single and multiple treatments with L-dihydroxyphenylalanine (L-DOPA) on dopamine receptor-G protein interactions and supersensitive immediate early gene responses in striata of rats after reserpine treatment or with unilateral nigrostriatal lesions.

We studied effects of L-dihydroxyphenylalanine (L-DOPA) treatment in rats following reserpine treatment or unilateral 6-hydroxydopamine (6-OHDA) injections into medial forebrain bundle. Quantitative in situ hybridization for mRNA's coding for the zinc finger immediate early gene (IEG) zif/268 or Jun family IEG jun b revealed that single L-DOPA injections accentuated IEG expression 3- to 7-fold in the dopamine (DA)-depleted striatum. This increased IEG response did not derive from any alterations in DA receptor-G protein coupling, assayed by DA stimulation of 35S-guanosine-5' (gamma-thio) triphosphate (35S-GTP-gamma-S) binding to striatal sections. Reserpine treatment increased both basal and maximal striatal DA-stimulated 35S-GTP-gamma-S binding. The augmented IEG responses to single L-DOPA treatments involved dependency on both D1 and D2 receptors and acutely to N-methyl-D-aspartate (NMDA) channels. Repetitive L-DOPA treatments yielded persistently elevated (zif/268) or additionally up-regulated (jun b) IEG response in the denervated striatum and down-regulated IEG responses in the control striatum. Degraded L-DOPA responses and appearance of involuntary movements after chronic L-DOPA use in advanced Parkinson's disease may derive from these IEG changes.

Animals↗
PubMed2000

The effect of reserpine, a modulator of multidrug efflux pumps, on the in vitro activity of tetracycline against clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) possessing the tet(K) determinant.

As part of a screening programme to identify modulators of multidrug efflux in methicillin resistant Staphyloccocus aureus (MRSA), we have validated our assays using the antihypertensive plant alkaloid reserpine. Clinical isolates of MRSA were resistant to tetracycline and shown to possess the tet(K) determinant which encodes for the Tet(K) efflux protein, which conferred high level resistance to tetracycline (MIC = 128 microg/mL). In the presence of reserpine, a known inhibitor of multidrug resistance (mdr) efflux pumps, this MIC was significantly reduced (MIC = 32 microg/mL).

Anti-Bacterial Agents↗
PubMed1978

Reserpine and breast cancer.

After a series of studies on the linkage of reserpine with breast cancer, both evidence and interpretation appeared to be in conflict. Our case-control survey of long-term, comprehensive records from the Kaiser Foundation Medical Care Program, on 108 hypertensive breast cancer cases and 324 hypertensive controls, matched by year of birth and by race, produces a significant positive association between reserpine use and breast cancer. However, the association vanishes upon further matching with respect to the year of the first hypertension diagnosis and the subsequent length of follow-up. We thus fail to support suspicions of causality.

Age Factors↗
PubMed1978

Formation of apical pseudopods by canine thyroid follicular cells: induction by thyrotropin and 5-hydroxytryptamine; antagonism by reserpine.

The role of biogenic amines in the activation of thyroid follicular cells by thyrotropin (TSH) was studied. 5-hydroxytryptamine (5-HT) was chosen as the amine to study and apical pseudopod formation, assessed by scanning electron microscopy, was used as the index of follicular cell activation. All experiments were done on dogs. TSH and 5-HT were both potent inducers of pseudopod formation. The action of TSH but not that of 5-HT was antagonized by the amine depleting drug reserpine. Reserpine depleted the thyroid of 5-HT in newborn, adolescent, and adult dogs. It is concluded that one or more biogenic amines, such as 5-HT, are probably involved in follicular cell activation by TSH.

Animals↗
PubMed1986

Time course of the changes of TH mRNA in rat brain and adrenal medulla after a single injection of reserpine.

A single injection of reserpine causes a long lasting enhancement of the activity of tyrosine hydroxylase (TH), the enzyme catalyzing the rate-limiting step in the biosynthesis of catecholamines. A sensitive method has been developed to assay both TH mRNA level and enzyme activity in tissue from a single rat. The time course of the induction was analysed in adrenals, locus coeruleus and substantia nigra. In both locus coeruleus and adrenals reserpine caused respectively 4.2- and 4.5-fold increase of TH mRNA which was maximal 2 days after drug injection. This increase is about twice that of the enzyme activity. No change was observed in substantia nigra. The effect lasted longer in locus coeruleus than in adrenal. In the latter, TH mRNA had almost returned to initial values at day 4 whereas at this time it is 3-fold higher in locus coeruleus and still significant at day 18. This result suggests that induction of TH results from an enhanced transcription of the TH gene. The time course difference between locus coeruleus and adrenals is most likely to result from a difference in the stability of TH mRNA in the two structures.

Adrenal Medulla↗
PubMed2004

Opioid-mediated modulation of calcium currents in striatal and pallidal neurons following reserpine treatment: focus on kappa response.

Previous work has shown that enkephalins target N-type calcium (Ca2+) channels in striatal and globus pallidus (GP) neurons, principally through activation of mu-like receptors. Here, we examined the effects of selective mu, delta, and kappa agonists on Ca2+ currents in striatal and GP neurons isolated from either control or reserpine-treated rats. In cells from control rats DAMGO and dynorphin (DYN) inhibited high-voltage-activated (HVA) Ca2+ currents preferentially in "medium-to-small" GP cells (likely to correspond to parvalbumin-negative cells). The kappa response was elicited by several agonists (DYN 17, DYN 13, BRL, U50-488-H), U50-488-H being the most effective (>30% maximal inhibition). U50-488-H affected both omega-CgTxGVIA-sensitive and nimodipine-sensitive Ca2+ conductances. The kappa-mediated effect (but not the mu response) was slow and blocked by chelerythrine, supporting the involvement of protein kinase C. In neurons from reserpinized rats we observed modest changes in the mu-inhibited fraction in small GP cells and a dramatic reduction of the kappa-sensitive fraction in principal striatal cells. These data imply that aminergic depletion alters opiate transmission differentially in the indirect and direct pathways. The suppression of the kappa response only in striatum reinforces the notion of an imbalance of endogenous opiates as relevant in extrapyramidal motor dysfunctions.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2001

Striatal cannabinoid CB1 receptor mRNA expression is decreased in the reserpine-treated rat model of Parkinson's disease.

High levels of both endocannabinoids and endocannabinoid receptors are present in the basal ganglia. Attention has recently focused on the role of endocannabinoids in the control of movement and in movement disorders of basal ganglia origin such as Parkinson's disease. We investigated CB1 cannabinoid receptor mRNA expression in the reserpine-treated rat model of Parkinson's disease using in situ hybridization. Reserpine treatment caused a topographically organized reduction in CB1 receptor mRNA expression in the striatum (ranging from 11.6% medially to 53.6% laterally and dorsally). No change in CB1 receptor mRNA expression was observed in the cerebral cortex or septum. This reduction in CB1 receptor mRNA expression may be secondary to increased endocannabinoid stimulation of the receptor as increased basal ganglia endocannabinoid levels have been shown to occur in this model of Parkinson's disease. The data support the idea that cannabinoid receptor antagonists may provide a useful treatment for the symptoms of Parkinson's disease.

Animals↗
PubMed2001

Multiple complexes involved in tyrosine hydroxylase mRNA stability in rat adrenal medulla, after reserpine stimulation.

A 28-nucleotide sequence within the 3'-untranslated region (3'UTR) of tyrosine hydroxylase (TH) mRNA has been suggested to influence the turnover rate of the TH messenger in vitro (W. R. Paulding and M. F. Czyzyk-Krzeska, 1999, J. Biol. Chem. 274, 2532-2538). In this study, we show that treatment with reserpine, a catecholamine-depleting drug which increases the stability of TH mRNA, allows the binding of a cytosolic protein to this 28-mer site in the TH 3'UTR in the rat adrenal medulla. An ex vivo kinetic analysis shows that the resulting 54-kDa ribonucleoprotein is early induced by reserpine. However, the formation of this complex is not coupled with the upregulation of TH mRNA, indicating that this 54-kDa complex could not be the unique factor accountable for the long-term stabilization of the TH messenger. Following this result we found that several other cis-acting elements, located in single-stranded stem loops within the secondary structure of TH 3'UTR, formed multiple complexes (43, 54, and 105 kDa) with cytosolic, polysome-associated, and also nuclear proteins. Our findings demonstrate that the messenger stability does not depend solely on the formation of a unique RNA-protein complex, but involves mechanisms with higher complexity implicating the interactions between posttranscriptional, nuclear RNA export, and translational processes.

3' Untranslated Regions↗
PubMed1990

Inhibitory effects of chlorogenic acid, reserpine, polyprenoic acid (E-5166), or coffee on hepatocarcinogenesis in rats and hamsters.

Four different experiments were performed in order to examine the modifying effects of chlorogenic acid (CA), reserpine, polyprenoic acid (E-5166), and coffee on chemical carcinogenesis in rats or hamsters. Experiment 1: The numbers of hyperplastic liver cell foci and the incidence of colon tumors in male and female Syrian golden hamsters given a single intravenous injection of methylazoxymethanol (MAM) acetate and then fed the diet containing 0.025% CA for 24 wk were significantly lower than those of hamsters given MAM acetate alone. Experiment 2: The incidence of altered hepatocellular foci in female ACI/N rats given N-2-fluorenylacetamide (FAA, 0.02% in diet) for 10 wk and reserpine (weekly subcutaneous injections, 1 microgram/g body weight) during or after (17 wk) FAA exposure was significantly lower than that of rats given FAA alone. Experiment 3: The number of hepatocellular foci in male ACI/N rats given 0.02% FAA diet for 13 wk and E-5166 by gavage (40 mg/kg body weight, 3 times/wk) for 16 wk after the end of FAA exposure was significantly smaller than that in rats given FAA diet alone. Experiment 4: Incidences of liver tumors and hepatocellular foci of rats given concurrent dietary administration of aminopyrine (0.01%) and sodium nitrite (0.1%) and coffee solution as a drinking water for 630 da were significantly lower than those of rats given aminopyrine and sodium nitrite. Thus, the tested compounds had inhibitory effects on chemical carcinogenesis in liver or colon.

Animals↗
PubMed1980

Effects of preceding sensibilization by reserpine and haloperidol on toxicity of dopaminergic agonists.

The effect of dopaminergic supersensitivity induced by repeated administration of neuroleptics on the toxicity of amphetamine in mice has been examined. As well as haloperidol, reserpine pretreatment increased the toxicity of amphetamine. Combined pretreatment did not cause a further increase of mortality following amphetamine. Dose response curves were not parallel, which might indicate different causes of death in naive and sensitized mice. Pretreatment with haloperidol did not change the toxicity of reserpine. The potentiating effects of neuroleptics on amphetamine toxicity may be connected with their ability to induce supersensitivity to dopaminergic agonists.

Amphetamine↗
PubMed1987

Inhibition of 5-hydroxytryptamine accumulation and deamination by substituted phenylalkylamines in hypothalamic synaptosomes from normal and reserpine-pretreated rats.

1. In the present study the abilities of different compounds to inhibit MAO inside and outside the serotonergic neurons, to inhibit the accumulation of 5-HT and to release 5-HT were separated by using different in vitro techniques. With these methods a number of substituted phenylalkylamines, which are reversible inhibitors of monoamine oxidase (MAO) type A, were characterized. 2. The compounds were examined regarding their ability to inhibit the accumulation of 5-HT and to inhibit MAO in the same synaptosomal preparation of hypothalamus from normal and reserpine-pretreated rats. The difference in the uptake of 14C-5-HT (0.1 mumol/l) in the absence and presence of citalopram (0.25 mumol/l) was taken as a measure of the accumulation into the serotonergic synaptosomes. The deamination of 14C-5-HT (0.1 mumol/l) in the presence of citalopram (0.25 mumol/l) was considered as that brought about outside the serotonergic synaptosomes, whereas the difference between the deamination in the absence and presence of citalopram was taken as the MAO activity inside the serotonergic synaptosomes. 3. Most of the phenylalkylamines were slightly more potent as MAO inhibitors outside serotonergic synaptosomes than as inhibitors of 5-HT accumulation in normal rats. The most potent MAO inhibitors, both in absolute terms and in comparison with uptake inhibitory potency, were the 2,6-dichloro-(FLA 365) and the phenylpropylene-(FLA 417) derivatives. 4. A difference in potency on the accumulation in synaptosomes from normal and reserpine-pretreated rats was found for many of the phenylalkylamines with the exception of FLA 365, FLA 417 and the 2,5-dimethyl derivative RAN 113.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Analysis of the nature of antagonism of the reserpine-induced hypothermia by imipramine.

Antagonism of reserpine-induced hypothermia is an animal model used in the screening of antidepressants. The activity of imipramine on this test is partly impaired by propranolol. This effect of imipramine was analyzed using specific adrenoceptor and 5-HT receptor blocking drugs in order to determine the nature of this effect of propranolol. The non-selective beta 1-beta 2 adrenoceptor antagonist, propranolol as the specific beta 1 adrenoceptor antagonist betaxolol, but not the specific beta 2 blocking drug DL-erythro-3-isopropylamino-1-(7-methyl-4-indanyloxy)-2-butanol hydrochloride 313.9 (ICI 118,551), partly antagonized the effect of imipramine at 30 min. None of the serotonin (5-HT) receptor antagonists, methysergide, metergoline, ritanserin and buspirone, impaired the effect of imipramine. On the contrary, methysergide alone antagonized reserpine-induced hypothermia and methysergide or metergoline increased the action of imipramine. Propranolol impaired neither the hypothermia induced by an agonist at the 5-HT 1A receptors: 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) nor the increase in spontaneous motor activity induced by an agonist at the 5-HT 1B receptors: 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1-H indole (Ru 24,969). It is concluded that the effect of propranolol is not the result of a blockade of 5-HT 1A, 5-HT 1B or 5-HT 2, but is in part due to blockade of beta 1 adrenoceptors.

Adrenergic beta-Antagonists↗