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PubMed1991

Analysis of the interaction of reserpine with actin by the photoaffinity labelling method.

The interaction of reserpine with one of the cytoskeletal proteins, actin, was analyzed by the photoaffinity labelling method using [3H]reserpine. Reserpine bound sufficiently to G- or oligomeric actin, but hardly to F-actin under the same experimental conditions. This result could be explained if reserpine binds to a specific region of the G-actin molecule that is responsible for actin-actin interactions. It is concordant with this idea that [3H]reserpine bound only to specific proteolytic fragments of actin. When reserpine was mixed with crude extracts of two kinds of tissues, chicken gizzard smooth muscle and bovine adrenal medulla, it bound to the 42 kDa protein of sodium dodecyl sulfate-polyacrylamide gel electrophoresis in both cases. Its molecular size and abundance suggest strongly that this 42 kDa protein is actin. The binding of reserpine to actin was inhibited by dopamine in a dose-dependent manner. These results suggest that actin could be one of the target molecules of reserpine.

Actins↗
PubMed2002

Concomitant development of oral dyskinesia and memory deficits in reserpine-treated male and female mice.

It has been suggested that reserpine-induced oral dyskinesia in rats may provide a new animal model of tardive dyskinesia. Both cognitive deficits and gender have been associated with the development of tardive dyskinesia. The aim of the present study was to investigate the effects of reserpine administration on the development of orofacial dyskinesia and on plus-maze discriminative avoidance task (DAT-an animal model of associative learning) in male and female mice. Male and female mice received 1.0 mg/kg reserpine or saline subcutaneously on day 1. On days 3, 6 and 8, the frequency of vacuous chewing movements (VCM) was quantified. On day 6, the DAT conditioning was performed, in a modified elevated plus-maze. In one of the enclosed arms, the animals received aversive stimulation (light and noise). On day 8, a test session was performed and the time spent by the animals in each of the enclosed arms was recorded. Our results showed that reserpine-treated male and female mice presented significantly higher VCM when compared with respective control groups in all observation days. On day 6, reserpine-treated female mice presented significantly higher VCM when compared with male mice injected with this drug. The DAT test performed on day 8 showed that the time spent in the aversive arm by saline-treated mice was significantly lower than the time spent in the non-aversive arm. This difference was not observed for reserpine-treated mice. Our results demonstrate the development of reserpine-induced oral dyskinesia in both male and female mice. While this oral dyskinesia is accompanied by a cognitive deficit in both genders, female mice tended to have more severe oral dyskinesia. It is suggested that reserpine-induced oral dyskinesia may provide a quick, simple and efficient mouse model of tardive dyskinesia.

Animals↗
PubMed1998

Alterations in Ca2+ storage and mobilization in submandibular acinar cells of reserpine-treated rats.

The present study investigated the effects of the catecholamine-depleting drug reserpine on cellular Ca2+ storage and mobilization in rat submandibular acinar cells. Adult rats received seven daily injections of reserpine (0.5 mg/kg) and inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ mobilization were measured in isolated submandibular acinar cells. Ultrastructural analysis demonstrated a significant reduction in rough endoplasmic reticulum (ER) and a dramatic accumulation of secretory granules in the cells of treated animals. Reserpine reduced acetylcholine (ACh)-stimulated IP3 formation by 46% and the initial increase in cytosolic Ca2+ concentration ([Ca2+]i) in response to ACh or thapsigargin was reduced by 21 and 56%, respectively. While norepinephrine (NE) did not induce significant IP3 formation, the [Ca2+]i response to NE was increased 360% by reserpine treatment. Reserpine treatment also enhanced the sustained [Ca2+]i increase following these stimuli. After stimulation with ACh or NE, exposure to ionomycin caused a further elevation in [Ca2+]i which was significantly larger in the cells of treated animals. After exposure to agonist + ionomycin, addition of monensin induced a third increase in [Ca2+]i which was significantly larger in cells of reserpine-treated animals. While capacitative Ca2+ entry was not altered, NE-activated Ca2+ influx was abolished after reserpine treatment. Reserpine treatment therefore alters IP3-sensitive and insensitive Ca2+ stores, non-capacitative Ca2+ influx and active Ca2+ transport in submandibular acinar cells of rats.

Acetylcholine↗
PubMed1990

Energetics of reserpine binding and occlusion by the chromaffin granule biogenic amine transporter.

The energetics of reserpine binding to the bovine adrenal biogenic amine transporter suggest that H+ ion translocation converts the transporter to a form which binds reserpine essentially irreversibly. Reserpine binding to bovine adrenal chromaffin granule membrane vesicles is accelerated by generation of a transmembrane pH difference (delta pH) (interior acid) or electrical potential (delta psi) (interior positive). Both components of the electrochemical H+ potential (delta mu H+) must be dissipated to block reserpine binding, and generation of either one stimulates the binding rate. Reserpine binding is less dependent than amine transport on the delta pH, suggesting that translocation of fewer H+ ions is required to expose the high-affinity site than are required for net transport. Bound reserpine dissociates very slowly, if at all, from the transporter. Binding is stable to 1% cholate, 1.5% Triton X-100, 1 M SCN-, and 8 M urea, but sodium dodecyl sulfate (0.035%) and high temperatures (100 degrees C) released bound reserpine, indicating that binding is noncovalent. The results raise the possibility that the transporter, by translocating one H+ ion outward down its concentration gradient, is converted to a form that can either transport a neutral substrate molecule inward or occlude reserpine in a dead-end complex.

Adenosine Triphosphatases↗
PubMed1993

Sensitization of P388 murine leukemia cells to epirubicin cytotoxicity by reserpine.

Reserpine, the crystalline active substance isolated from the Rauvolfia plant, produces a characteristic vasodepressor effect in hypertensive patients. Apart from its antihypertensive property, reserpine also possesses transquillising and vasodepressor action, hence it is employed as supportive therapy in the treatment of cardiac disorders. Doxorubicin is a potent anticancer agent, the use of which is limited by its cumulative dose-dependent cardiotoxicity. Epirubicin is a derivative of doxorubicin having more favourable therapeutic index than doxorubicin and possessing less hematologic and cardiac toxicity at comparable doses. The data presented in this paper show the effect of reserpine as a chemosensitizer, when used in combination with epirubicin on P388 murine leukemia cells sensitive (P388/S) and resistant to doxorubicin (P388/DOX) cells. Inhibition of 3H-TdR incorporation into DNA was used as an index of the cytotoxic effects of drug when used alone or in combination. The combination of reserpine (1 microM) and epirubicin (1.7, 8.6 and 17.2 microM) indicated a significant enhancement in the DNA biosynthesis inhibition in P388/S and P388/DOX cell lines. The most prominent feature of the multidrug-resistant cell is the reduced accumulation of the drug intracellularly. P388/DOX cells showed less accumulation of epirubicin in the cell as compared to that of the parental cell line. Further studies demonstrated that reserpine significantly enhanced the intracellular accumulation of epirubicin in both the cell lines. The nature of DNA damage caused by the combination of reserpine and epirubicin was irreversible when studied in P388/DOX cell line. The combination of reserpine (5mg/kg) and epirubicin (1mg/kg) significantly potentiated the antitumor activity of epirubicin in P388/DOX tumor bearing mice. These studies suggest that reserpine can be used as an adjuvant in the cancer chemotherapy to potentiate the antiproliferative activity of anticancer drugs.

Animals↗
PubMed1969

Effects of reserpine on the disposition of sympathomimetic amines in vascular tissue.

1. The effects of reserpine pretreatment on the intrinsic inactivation of low concentrations of phenylephrine and noradrenaline in strips of rabbit thoracic aorta were assessed by measuring the rates of relaxation, after oil immersion to prevent loss of active amine by diffusion into the surrounding medium.2. Reserpine pretreatment considerably augmented the amplitude of responses to low concentrations of phenylephrine, noradrenaline and nordefrine (Cobefrine).3. Reserpine pretreatment did not reduce the overall rate of inactivation of either phenylephrine or noradrenaline, but it did appear to decrease the contribution of uptake and storage, measured as an increased effect of enzyme inhibition and a decreased effect of cocaine on the rate of inactivation.4. The role of catechol-O-methyl transferase (COMT), but not that of monoamine oxidase (MAO), in terminating the action of noradrenaline was increased in strips from animals pretreated with reserpine. Thus it appears that interference with intraneuronal storage diverts active amine to inactivation by COMT in vascular tissue, rather than by MAO as has been previously suggested.5. As in preparations not treated with reserpine, inhibition of MAO alone had little effect on the rate of inactivation of noradrenaline, and this enzyme appears to function predominantly as an alternate pathway of little importance as long as COMT activity is unimpaired. Enzymatic processes accounted for about 85 and 70% of the inactivation of a low concentration of noradrenaline in reserpine pretreated and untreated preparations, respectively.6. Cocaine potentiated responses to noradrenaline and phenylephrine as effectively in reserpine pretreated as in untreated preparations, and inhibition of the pathways of enzymatic inactivation did not appreciably decrease the potentiation produced by this agent.7. The present results cannot be explained by the hypothesis that interference with amine inactivation by nerve uptake and storage is responsible for the potentiation of responses to noradrenaline or phenylephrine by either reserpine or cocaine, and emphasize the unrealiability of potentiation as an index of interference with mechanisms involved in terminating the action of sympathomimetic amines.

Animals↗
PubMed1989

The thermogenic actions of alpha 2-adrenoceptor agonists in reserpinized mice are mediated via a central postsynaptic alpha 2-adrenoceptor mechanism.

1. The dose-related effects of the selective alpha 2-adrenoceptor agonists clonidine, UK-14,304 and B-HT 933 on the body temperature of untreated and reserpine-treated mice were investigated. 2. In untreated mice all three agonists induced a dose-related hypothermia. The highest doses of UK-14,304 and B-HT 933, 3 and 100 mg kg-1 respectively, elicited a marked (10 degrees C) hypothermia, whereas the maximal hypothermic effect of clonidine (5.5 degrees C) was less pronounced and reached a plateau at a dose of 0.5 mg kg-1 i.p. 3. Reserpine (2.5 mg kg-1, s.c.) induced a marked hypothermia in the mouse; 18 h after injection body temperature had decreased to only slightly (0.5-1.5 degrees C) above ambient (19 degrees C). 4. All three alpha 2-agonists produced a partial dose-related reversal of reserpine-induced hypothermia; maximal thermogenic responses (9-10 degrees C increases in body temperature) were elicited by doses of 0.2, 0.5 and 16 mg kg-1 i.p. of clonidine, UK-14,304 and B-HT 933 respectively, and the log dose-response curves for all 3 agonists were bell-shaped. 5. Following intracerebroventricular administration to reserpine-treated mice, the thermogenic response to clonidine was more rapid in onset, and the agonist was 20 fold more potent than when injected i.p. 6. The selective alpha 2-adrenoceptor antagonists, idazoxan (0.05-0.5 mg kg-1), Wy 26392 (0.3-5.0 mg kg-1) and yohimbine (0.1-1.6 mg kg-1) given orally attenuated the thermogenic responses to all 3 agonists in reserpinized mice in a dose-related manner. Pretreatment with a single dose of idazoxan (0.3 mg kg-1, orally) elicited a 6 fold parallel shift to the right in the dose-response curve to clonidine. 7. The selective alpha 1-adrenoceptor antagonists, prazosin (10 mg kg-1) and indoramin (3-10 mg kg-1), and the beta-adrenoceptor antagonist, propranolol (10 mg kg-1), only partially attenuated the thermogenic responses to the alpha 2-agonists in reserpinized mice. These effects were variable and not clearly dose-related. 8. Pretreatment of reserpinized mice with the catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine, markedly attenuated (60-95%) the thermogenic response to the noradrenaline uptake inhibitor, desipramine (0.13-12.5 mg kg-1, i.p.), but only slightly reduced (10-35%) that to clonidine (0.032-0.5 mg kg-1, i.p.). 9. These results suggest that alpha2-adrenoceptor agonists reverse reserpine-induced hypothermia via a central mechanism involving activation of postsynaptic alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1978

Effect of (+)-amphetamine on the retention of 3H-catecholamines in slices of normal and reserpinized rat brain and heart.

The effect of reserpine on the inhibition by (+)-amphetamine and cocaine of the accumulation of 3H-dopamine (DA) in striatal slices and 3H-noradrenaline (NA) in slices of cerebral occipital cortex and heart atrium of rats and the release of 3H-amines from these tissues were examined. Reserpine (5 mg/kg intraperitoneally) was injected 18 hours before the experiments. It was found that reserpine markedly enhanced the in vitro potency of amphetamine in the striatum and heart but only slightly in the cortex. After administration in vivo (+)-amphetamine was about 10 time more potent in reducing the amine accumulation in the cortex as in the striatum. Reserpine enhanced the effect in both regions. The inhibitory potency of cocaine in vitro was unchanged by reserpine in the striatum but was reduced in the cortex and heart. Reserpine did not change the inhibitory potency of desipramine in the cortex and heart. The release of the 3H-amines by (+)-amphetamine was enhanced by reserpine in the striatum and heart but the small release produced in the cortex was not increased. The release produced by cocaine was similarly enhanced by reserpine but cocaine was much less active than (+)-amphetamine. The results indicate that (+)-amphetamine and cocaine inhibit the amine accumulation by different mechanisms.

Animals↗
PubMed1979

Effect of a single injection of reserpine on kinetics of 3H-dexamethasone binding to receptors of the cat hypothalamus and hippocampus.

Cats were injected intraperitoneally with reserpine (5 mg/kg) or saline and sacrificed 16 h later. Hypothalamic and hippocampal cytosols were assayed for the kinetics of 3H-dexamethasone (3H-DM) binding. A parallel series was performed in which saline-injected cats were infused via venocatheter with hydrocortisone (HC). Reserpine-injected cats were infused with saline. The hypothalamic cytosol of reserpinized cats showed a marked decrease in 3H-DM binding capacity relative to that from saline-treated cats. Hippocampal cytosol 3H-DM binding capacity was unaffected by reserpinization. Infusion of high levels of HC reduced the amount of 3H-DM binding in the hypothalamus, but did not account for all the reduction found after reserpine treatment. HC infusion had no effect on hippocampal binding capacity. Reserpine treatment did not change the dissociation constant differences between the two brain regions. The data suggest that depletion of neurotransmitters by reserpine treatment from the hypothalamus, but not the hippocampus, significantly reduces the number of 3H-DM binding sites and that such a reduction is due, in part, to the effects of reserpine and not to high circulating levels of HC.

Animals↗
PubMed1981

Terminals of reserpine-sensitive vasopressin-neurophysin neurons in the external layer of the rat median eminence.

The indirect immunofluorescence technique was used to examine the pharmacology associated with reserpine-induced alterations in vasopressin and neurophysin (VP/NP) immunoreactivity in the external layer of the median eminence in the rat. Twenty-four hours after injection of reserpine, a selective, marked depletion of VP/NP immunoreactivity from the external layer is apparent. Pretreatment with the monoamine oxidase inhibitors, pargyline and tranylcypromine, prevents the depleting effect of reserpine, indicating that the acute effect of reserpine is mediated by monoamines. Acute intraventricular treatment with 6-hydroxydopamine, but not 5,7-dihydroxytryptamine, mimicked the reserpine effect, suggesting that catecholamines mediate reserpine depletion of VP/NP immunoreactivity from the external layer. The experimental results are consistent with a regulatory model in which catecholamines tonically inhibit VP/NP release from terminals in the external layer of the median eminence. Although the studies do not definitively determine the functional relationship between VP and ACTH, the anatomical location of these terminals, the dramatic change in the VP/NP content of these terminals in response to reserpine, and the lack of a response to dehydration suggest that this pool of vasopressin may contribute to ACTH hypersecretion in response to reserpine.

Animals↗
PubMed1983

Pharmacological studies on supersensitization. XII. Inhibitory effect of reserpine on tripelennamine-, N,N-dimethyl-N',N'-dibenzylethylenediamine- and N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine-induced supersensitivity of isolated vas deferens of guinea pig to acetylcholine.

Effects of tripelennamine, N,N-dimethyl-N',N'-dibenzylethylenediamine (DBED) and N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine (DBPD) on the isotonic contractions of isolated vas deferens of intact and reserpinized guinea pigs to acetylcholine were examined. Increase in sensitivity to acetylcholine induced by tripelennamine, DBED and DBPD was attenuated remarkably by reserpine. Tripelennamine- and DBED-induced increases in Ca2+-contractions were not affected by reserpine. Acetylcholine-contractions in Ca2+-free Tyrode solution were inhibited by reserpine, but K+-contractions in Ca2+-free Tyrode solution were not affected by reserpine. Tripelennamine- and DBED-induced increases in acetylcholine- and K+-contractions in Ca2+-free Tyrode solution were attenuated or abolished by reserpine. DBPD decreased cholinesterase activity of vas deferens of guinea pig, but DBED did not. These results suggest that, although the Ca2+-storage site utilized for acetylcholine-contraction is different from that for K+-contraction, tripelennamine- and DBED-induced increase in Ca2+-release from superficial Ca2+-binding sites induced by acetylcholine and K+ is inhibited by reserpine. It is also estimated that DBPD-induced supersensitivity to acetylcholine might be due to the inhibition of cholinesterase activity. However, the mechanism of inhibition of DBPD-induced supersensitivity by reserpine remained obscure.

Acetylcholine↗
PubMed1978

Effects of several monoamine-related compounds on the reserpine-induced spikes recorded from the medial nucleus trapezoides in rabbits.

Effects of several monoamine-related compounds on the reserpine-induced spikes recoreded from the medial nucleus Trapezoides (reserpine-induced Tr spikes) in rabbits were investigated. 5HTP (30--50 mg/kg, i.p.) showed marked suppression of reserpine-induced Tr spikes. Parachlorophenylalanine (PCPA) alone induced spikes similar to reserpine-induced Tr spikes after repeated doses (250 mg/kg twice daily for 3 successive days). A marked enhancement of the generation of reserpine-induced Tr spikes was elicited, when reserpine was given to rabbits pretreated with PCPA. L-DOPA (30--50 mg/kg, i.p.) showed a slight but significant suppressive action 20 to 40 min after injection. alpha-methyl-p-tyrosine (alpha-MT) (200 mg/kg, i.p.) produced no significant change within 6 hr, but did show a marked facilitatory effect on the generation of the spikes when reserpine was given to rabbits pretreated with alpha-MT. alpha-methyl-metatyrosine (alpha-MMT) (100 mg/kg, i.v.) caused a long-lasting, marked suppression. These findings suggest that both catecholamines and 5HT have a suppressive action on the generation of reserpine-induced Tr spikes.

5-Hydroxytryptophan↗
PubMed1987

Modulation in vitro and in vivo of ACNU resistance in a subline of C6 glioma with reserpine.

Reserpine enhanced in vitro the cytotoxicity of 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) in both the C6 glioma and its ACNU-resistant subline, C6/ACNU. Reserpine also enhanced the chemotherapeutic effect of ACNU in C6/ACNU-bearing (C6/ACNU-meningeal gliomatosis) rats, in which ACNU resistance could be modulated by combined ACNU and reserpine therapy. When 10 microM reserpine was added to ACNU in culture, the concentration of drug required for 50% inhibition of cell growth (IC50) of ACNU for C6/ACNU cells decreased to the level of that for C6 cells. When 20 microM reserpine was added to the culture, intracellular uptake of ACNU in C6/ACNU cells increased further and the efflux of the drug from the cells decreased. In in vivo experiments in rats, combined chemotherapy with ACNU (1 mg/kg) and reserpine (250 micrograms/kg) by intrathecal injection significantly increased the life span of the rats as compared to results with ACNU chemotherapy alone. The enhanced cytotoxicity of ACNU in ACNU-resistant glioma cells in vitro and in vivo may be explained by the increase of intracellular concentration of ACNU resulting from the inhibition of ACNU efflux from the resistant cells by reserpine. It was concluded that ACNU resistance could be modulated in vitro and in vivo by combined therapy with ACNU and reserpine.

Animals↗
PubMed1976

Effects of prenatal reserpine administration on development of the rat adrenal medulla and central nervous system.

Reserpine (1 mg/kg s.c.) was administered to pregnant rats at different periods of gestation. Rats born to mothers who received reserpine on days 6, 5 and 4 or 4, 3 and 2 before delivery showed early postnatal adrenal catecholamine depletion, an effect which can be attributed to a direct action of the drug; however, at no time was induction of tyrosine hydroxylase or dopamine beta-hydroxylase observed. Administration of reserpine on days 9, 8 and 7 before delivery did not alter postnatal adrenal catecholamine levels in the offspring but produced permanent elevations in enzyme activities and vesicular amine uptake beginning at 10 days of age. Studies utilizing direct stimulation with nicotine indicated that the inherent responsiveness of the adrenal medulla itself was the same in control and reserpine-exposed pups. These data all suggest that sympathoadrenal tone has been permanently increased in the offspring of rats which have been exposed to reserpine early in gestation. In the brain, administration of reserpine on days 6, 5 and 4 before delivery resulted in a delay in early postnatal development of brain weight and synaptosomal uptake mechanisms, and at later stages subnormal tyrosine hydroxylase activities. When reserpine was given on days 9, 8 and 7 before delivery, only the deficiency in tyrosine hydroxylase was seen. These studies indicate that long-lasting changes in both peripheral and central nervous system catecholamine disposition can be produced by prenatal reserpine administration.

Adrenal Medulla↗
PubMed1990

Adaptive mechanisms of striatal D1 and D2 dopamine receptors in response to a prolonged reserpine treatment in mice.

Mice receiving reserpine (1 mg/kg/day) during 5 days develop behavioral supersensitivity. To study the possible molecular correlates of these adaptive changes we compared binding parameters of D1 and D2 receptors and adenylate cyclase activity in striata from normal and reserpinized mice. Saturation curves using [3H]SCH 23390 showed no changes in maximum binding capacity (Bmax) or Kd of striatal D1 receptors taken from control or 5 days reserpine-treated mice. However, [3H]spiperone saturation curves showed a 31% increase in D2 receptors Bmax with no changes in Kd. Dopamine competition of [3H]SCH 23390 and [3H]spiperone binding in mouse striatum was also performed. Analysis of data by LIGAND showed that dopamine recognizes two subpopulations for D1 and for D2 receptors. The proportion of receptors in the high affinity state (D1high and D2high) were increased in reserpine-treated animals. The addition of 100 microM GTP produced a complete conversion of D1high and D2high receptors into their low-affinity states in striata from control and reserpinized mice. Five days of reserpine treatment increased basal adenylate cyclase activity of mouse striatum in the presence of Mn++ or Mg++ ions. Concentration curves with dopamine, NaF or forskolin revealed shifts to the left and higher maximum responses without changes in EC50 values in striata from reserpinized mice. Thus, a prolonged reserpine treatment produces marked changes in D1 and D2 receptors increasing the proportion of high affinity state subpopulations and the total Bmax of D2 receptors. Also, dopamine function may be enhanced through an increment of the catalytic component of striatal adenylate cyclase.

Adenylyl Cyclases↗
PubMed1985

5-Hydroxytryptamine release in vivo from a cytoplasmic pool: studies on the 5-HT behavioural syndrome in reserpinized rats.

Treatment of rats with reserpine in order to disrupt vesicular amine storage reduces 5-hydroxytryptamine (5-HT) levels throughout brain by 90-95%. Despite the drastic reduction in brain 5-HT content by reserpine, the 5-HT releasing drug p-chloramphetamine (PCA) produces a behavioural syndrome in reserpine-treated rats which is not different from that observed in normal animals given PCA. Prior treatment of reserpinized rats with p-chlorophenylalanine (PCPA), the irreversible tryptophan hydroxylase inhibitor which inhibits the synthesis of new 5-HT, prevents the PCA-induced behavioural syndrome. The 5-HT receptor antagonist methergoline, blocks the PCA effect in reserpine-treated rats. Treatment of reserpinized rats with pargyline, a non-selective inhibitor of monoamine oxidase, in order to increase cerebral 5-HT levels, shifts the PCA dose-response curve for inducing the 5-HT behavioural syndrome to the left. The specific 5-HT uptake blocker, fluoxetine, protects normal and reserpine-treated rats from the 5-HT depleting effects of PCA but does not always prevent the PCA-induced 5-HT behavioural syndrome. These results indicate that PCA releases 5-HT into the synapse from a small cytoplasmic pool which is resistant to reserpine and suggest that this newly synthesized compartment of 5-HT represents the 'functional' transmitter pool.

Animals↗
PubMed1982

Influence of iproniazid on the combination effect of reserpine with antitumor agents on l1210.

The influence of two antidepressants, iproniazid and imipramine, was examined on the antileukemic combination effect of reserpine with 1-gamma-chloropropyl-2-chloromethylpiperidine hydrobromide (CAP-2), mitomycin C, or vinblastine on L1210. While reserpine synergistically increased the life span at the dose of 2.5 mg/kg in combination with these antitumor agents, the mice given reserpine showed considerable reduction of food intake and hypothermia. Iproniazid reduced all these effects of reserpine, while imipramine slightly potentiated hypothermia among these effects of reserpine. Starvation scarcely influenced the effect of the antitumor agents. On the other hand, reserpine also enhanced the antiproliferating effect of CAP-2 against L1210 cells in vitro. Iproniazid did not influence the combined antiproliferating effect of these agents in vitro. These results indicate that iproniazid reduced the antileukemic combination effect of reserpine with antitumor agents through an antireserpic effect such as inhibition of hypothermia. Therefore, it seems likely that the antileukemic combination effect of reserpine is closely related to the marked hypothermia, and only partially related to the direct effect on L1210 cells.

Animals↗
PubMed1981

Interactions of reserpine and morphine on rat intestinal transit.

A study was designed to examine the interactions of reserpine and morphine on rat intestinal transit. Intestinal transit was determined in adult male rats by measuring the progression of an intraduodenally administered bolus (0.2 ml) or radioactive chromium (Na2(51)CrO4, 0.5 microCi) solution through the small intestine. Reserpine phosphate and morphine sulfate were administered either s.c. at 5 mg/kg or intracerebroventricularly (i.c.v.) at 50 and 30 micrograms (total dose), respectively. Reserpine given s.c. 16 hr before testing enhanced intestinal transit when given alone and diminished the intestinal antipropulsive effects of morphine given s.c. or i.c.v. Reserpine given i.c.v. 8 hr before testing did not alter the intestinal effects of morphine given s.c. or i.c.v. Neostigmine methylsulfate (0.1 mg/kg) given s.c. did not alter intestinal transit by itself but antagonized the inhibition of intestinal transit produced by morphine given s.c. Atropine sulfate (6 mg/kg) given s.c. did not affect intestinal transit by itself, nor did it antagonize the intestinal effects of s.c. administered morphine. However, atropine inhibited enhanced intestinal transit after reserpine given s.c. and restored the inhibitory effect of peripheral morphine on intestinal transit in animals pretreated with peripheral neostigmine or reserpine. The results suggest that reserpine inhibits the central and peripheral antidiarrheal effects of morphine by acting peripherally. Reserpine may antagonize the intestinal antipropulsive effects of morphine in the rat by directly or indirectly activating muscarinic cholinergic receptors.

Animals↗