Relaxant effects of a hydroalcoholic extract of Ruta graveolens on isolated rat tracheal rings

BACKGROUND: Ruta graveolens L. (R. graveolens) is a medicinal plant employed in non-traditional medicines that has various therapeutic properties, including anthelmintic, and vasodilatory actions, among others. We evaluated the trachea-relaxant effects of hydroalcoholic extract of R. graveolens against potassium chloride (KCl)- and carbachol-induced contraction of rat tracheal rings in an isolated organ bath. RESULTS: The results showed that the airway smooth muscle contraction induced by the depolarizing agent (KCl) and cholinergic agonist (carbachol) was markedly reduced by R. graveolens in a concentration-dependent manner, with maximum values of 109 ± 7.9 % and 118 ± 2.6 %, respectively (changes in tension expressed as positive percentages of change in proportion to maximum contraction), at the concentration of 45 µg/mL (half-maximal inhibitory concentration IC50: 35.5 µg/mL and 27.8 µg/mL for KCl- and carbachol-induced contraction, respectively). Additionally, the presence of R. graveolens produced rightward parallel displacement of carbachol dose-response curves and reduced over 35 % of the maximum smooth muscle contraction. CONCLUSIONS: The hydroalcoholic extract of R. graveolens exhibited relaxant activity on rat tracheal rings. The results suggest that the trachea-relaxant effect is mediated by a non-competitive antagonistic mechanism. More detailed studies are needed to identify the target of the inhibition, and to determine more precisely the pharmacological mechanisms involved in the observed biological effects.

Pharmacological characterization of the relaxant effect induced by adrenomedullin in rat cavernosal smooth muscle

The aim of the present study was to determine the mechanisms underlying the relaxant effect of adrenomedullin (AM) in rat cavernosal smooth muscle (CSM) and the expression of AM system components in this tissue. Functional assays using standard muscle bath procedures were performed in CSM isolated from male Wistar rats. Protein and mRNA levels of pre-pro-AM, calcitonin receptor-like receptor (CRLR), and Subtypes 1, 2 and 3 of the receptor activity-modifying protein (RAMP) family were assessed by Western immunoblotting and quantitative real-time polymerase chain reaction, respectively. Nitrate and 6-keto-prostaglandin F1α (6-keto-PGF1α; a stable product of prostacyclin) levels were determined using commercially available kits. Protein and mRNA of AM, CRLR, and RAMP 1, -2, and -3 were detected in rat CSM. Immunohistochemical assays demonstrated that AM and CRLR were expressed in rat CSM. AM relaxed CSM strips in a concentration-dependent manner. AM22-52, a selective antagonist for AM receptors, reduced the relaxation induced by AM. Conversely, CGRP8-37, a selective antagonist for calcitonin gene-related peptide receptors, did not affect AM-induced relaxation. Preincubation of CSM strips with NG-nitro-L-arginine-methyl-ester (L-NAME, nitric oxide synthase inhibitor), 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, quanylyl cyclase inhibitor), Rp-8-Br-PET-cGMPS (cGMP-dependent protein kinase inhibitor), SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole, selective cyclooxygenase-1 inhibitor], and 4-aminopyridine (voltage-dependent K+ channel blocker) reduced AM-induced relaxation. On the other hand, 7-nitroindazole (selective neuronal nitric oxide synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), H89 (protein kinase A inhibitor), SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine, adenylate cyclase inhibitor], glibenclamide (selective blocker of ATP-sensitive K+ channels), and apamin (Ca2+-activated channel blocker) did not affect AM-induced relaxation. AM increased nitrate levels and 6-keto-PGF1α in rat CSM. The major new contribution of this research is that it demonstrated expression of AM and its receptor in rat CSM. Moreover, we provided evidence that AM-induced relaxation in this tissue is mediated by AM receptors by a mechanism that involves the nitric oxide-cGMP pathway, a vasodilator prostanoid, and the opening of voltage-dependent K+ channels.

Action mechanism of the monoterpenes (+)-pulegone and 4-terpinyl acetate in isolated guinea pig ileum / Mecanismo de accion de los monoterpenos (+)-pulegona y acetato de 4-terpinil en íleon aislado de cobayo

Recent studies have shown the spasmolytic activity of p-menthane monoterpenes (+)-pulegone and 4-terpinyl acetate (4-T) in guinea pig ileum. Since the action mechanism of these monoterpenes in intestinal smooth muscle is unknown, the present study was conducted to characterize their relaxant mechanism in isolated guinea pig ileum. We tested the involvement of voltage-dependent calcium and potassium channels and muscarinic antagonism. Both the monoterpenes caused a shift in the calcium curve to the right with reduction in the maximum effect. Pretreatment with tetraethylammonium chloride partially inhibited relaxation produced by both 4-T and (+)-pulegone. Both compounds caused a shift in the bethanechol curve to the right with reduction in the maximum effect. The results of this study indicate that the mechanisms of action of the smooth muscle relaxant monoterpenes (+)-pulegone and 4-T possibly involve the partial blockade of calcium channels, the activation of potassium channels, and the non-competitive antagonism of muscarinic receptors.

Estudios recientes han demostrado la actividad espasmolítica de los monoterpenos p-mentano de (+)-pulegona y acetato de 4-terpinilo (4-T) en el íleon de cobayo. Dado que el mecanismo de acción de estos monoterpenos en el músculo liso intestinal es desconocido, el presente estudio se llevó a cabo para caracterizar su mecanismo relajante en íleon aislado de conejillo de indias. Hemos probado la participación de tanto los canales calcio dependiente de voltaje como los canales de potasio y antagonistas muscarínicos. Ambos monoterpenos causaron un desplazamiento en la curva de calcio a la derecha con la reducción en el efecto máximo. El tratamiento previo con cloruro de tetraetilamonio inhibe parcialmente la relajación producida por tanto 4-T y (+)-pulegona. Ambos compuestos causaron un cambio en la curva de betanecol a la derecha con la reducción en el efecto máximo. Los resultados de este estudio indican que los mecanismos de acción de los monoterpenos relajantes del músculo liso (+)-pulegona y 4-T posiblemente implican el bloqueo parcial de los canales de calcio, la activación de los canales de potasio, y el antagonismo no competitivo de los receptores muscarínicos.

Spasmogenic and spasmolytic activities Onosma griffithii Vatke

Methanolic extract of Onosma grifflthii and its fractions were evaluated for possible effects on rabbits' jejunum preparations. Rabbits of either sex [weight 1.5-2.0 kg] were used in experiments. Studies were carried out on rabbits' jejunum preparations. Crude methanolic extract of Onosma griffithii [Meth.OG] was tried in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on rabbits' jejunum preparations. Meth.OG was also tried on KCl-induced contractions to explain its possible mode of actions in the presence and absence of atropine [0.03 microM]. Fractions of Meth.OG were tried in similar manner. Calcium chloride curves were constructed for Meth.OG treated tissues that were compared with curves constructed for verapamil in same fashion. Preliminary phytochemical screening of the plant was also performed. Meth.OG increased the amplitude of spontaneous activity of rabbits' jejunum preparations at concentrations of 0.1, 0.3 and 1.0 mg/ml. However, spasmolytic effects were observed at higher concentrations 3.0, 5.0 and 10.0 mg/ml. Mean EC[50] values [mg/ml], respectively, in absence and presence of atropine were 7.5 +/- 0.25 [6.9-8.4, n=6] and 3.0 +/- 0.17 [2.3-3.5, n=6, P<0.05]. Mean EC[50] values, respectively, for effects on spontaneous and KCl-induced contractions were 7.5 +/- 0.25 [6.9-8.4, n=6] and 7.3 +/- 0.35 [6.25-8.2, n=6, p<0.05]. rc-Hexane, chloroform and ethyl acetate fractions showed their respective EC[50] values [mg/ml] 9.7 +/- 0.25 [8.6-10.2, n=6], 4.0 +/- 0.2 [3.5-4.6, n=6] and 1.07 +/- 0.093 [0.78-1.5, n=6]. EC[50] values for calcium chloride curves in presence of 0.3 mg/ml Meth.OG were - 2.27 +/- 0.038 [- 2.4 to - 2.10, n=6] vs. control - 2.78 +/- 0.04 [-2.9 to - 2.6, n=6,P<0.05] Log [Ca[++]]M. Comparing with curves of calcium chloride constructed in presence of 0.1 juM verapamil, the EC[50] [log [Ca[++]] M] values were - 1.82 +/- 0.087 [- 2.0 to - 1.65, n=6] vs. control - 2.64 +/- 0.089 [- 2.9 to - 2.4, n=6] demonstrated a right shift [p<0.05]. Meth.OG tested positive for terpenes, saponins, sterols, flavonoids and carbohydrates. We concluded that the relaxant effect of Meth.OG is exerted through blocking of calcium channels. However,

butanolic and aqueous fractions produced spasmogenic effects that require further work for isolation of pharmacologically active substances

Study of drotaverine on first stage of labour and pregnancy outcome.

A prospective randomised study of 200 women with spontaneous onset of labour was carried out in 100 women who were given 40mg of drotaverine hydrochloride intravenously at > or = 3cm dilatation of the cervix, the other 100 were taken as control. The effects of the drug on the progress and outcome of labour were noted. The mean durations of active phase of labour in primigravida and multigravida were 148.9 minutes and 99.5 minutes in drotaverine group whereas in control group were 331.6 minutes and 227.9 minutes respectively. It was concluded that drotaverine is highly effective in reducing the duration of active phase of labour by hastening cervical dilatation, more effective when given in more dilated cervix than with less dilatation and more effective in multigravida than in primigravida. There was no interference with uterine contractility and no increase in operative delivery. It reduces the incidence of traumatic postpartum haemorrhage by reducing the incidence of cervical tear. It is a safe drug for the mother as well as for the baby.

Mechanism of spasmolytic activity of a fraction of Sarcostemma brevistigma Wight.

The effect of chloroform soluble fraction (F-A) of twigs of Sarcostemma brevistigma on contractions induced by KCl, histamine, and acetylcholine in the isolated guinea pig ileum and taenia coli smooth muscles has been evaluated. F-A (19.5 microg/ml) significantly inhibited the contraction induced by 40 mM KCl to the extent of 87.6% in the isolated guinea pig ileum. In the isolated guinea pig ileum, F-A (64.3 and 59.2 microg/ml) significantly inhibited the contractions induced by acetylcholine and histamine to the extent of 85 and 83% respectively. In the isolated guinea pig taenia coli, F-A (65.2 microg/ml) significantly inhibited the contraction induced by 40 mM KCl to the extent of 96.0%. The inhibitory effect of F-A (40 microg/ml) on the isolated guinea pig taenia coli was reduced by Bay K 8644 (10(-6) M) to the extent of 61.6 from 73.6%. These results suggest that the F-A may exhibit smooth muscle relaxant activity by blocking the Ca2+ channels.

Modulatory effect of diclofenac on antispasmodic effect of pitofenone in cholinergic spasm.

Biliary, ureteric and intestinal colic are extremely common clinical conditions associated with smooth muscle spasm. In the present study, antispasmodic activity was carried out against acetylcholine (10-640 ng/ml)-induced contractions on guinea pig ileum. Acetylcholine (10-640 ng/ml) induced concentration-dependent contraction of smooth muscle. Diclofenac, in varying concentration (9.4 x 10(-5) mol/l and 14.1 x 10(-5) mol/l) shifted the concentration response curve of acetylcholine to the right without suppressing the maximal response. However, in higher concentration diclofenac (18.9 x 10(-5) mol/l) blocked the response in an unsurmountable fashion. Further, analgin (11.09 x 10(-5), 16.63 x 10(-5) and 22.18 x 10(-5) mol/l) in equimolar concentrations did not alter the concentration response curve of acetylcholine, but in higher concentration analgin (44.36 x 10(-5) mol/l) also blocked the response in an unsurmountable fashion. Pitofenone (2.5 x 10(-6) mol/l) also, shifted the concentration response curve of acetylcholine to right in a parallel fashion with no change in maximal response. The present study confirms the potent antispasmodic activity of diclofenac-pitofenone combination in comparison to analgin-pitofenone in molar equivalent concentration (in comparison to diclofenac) against acetylcholine-induced contractions of guinea pig ileum.

Efficient clonal propagation method for Decalepis hamiltonii, an endangered shrub, under the influence of phloroglucinol.

A highly efficient two stage protocol was developed for induction of multiple shoots from single node in vitro shoot tip explants of Decalepis hamiltonii. It was found that phloroglucinol (PG) had synergistic effect on shoot multiplication when added with N6-benzyladenine and gibberellic acid. This protocol uses PG for both multiple shoot induction from nodal explants, elongation of primary shoots and initiation of adventitious shoot formation from primary shoots, which was more in presence of triacontanol (TRIA). Maximum number of shoots per culture was observed on the medium containing N6-benzyladenine (1.1 microM; BA), GA3 (5.8 microM) and PG (800 microM). Sub-culturing of the shoots onto MS medium containing optimum concentration of BA (5.6 microM), PG (200 microM) and TRIA (0.011 microM) produced elongated shoots along with secondary shoot formation. The long shoots were rooted on alpha-naphthalene acetic acid (5.38 microM; NAA) and PG (400 microM) containing medium. The rooted plantlets were hardened and their field survival rate was 80-90%.

Antibacterial potential of an antispasmodic drug dicyclomine hydrochloride.

BACKGROUND & OBJECTIVES: Several compounds are known to possess antimicrobial activity in addition to their predesignated pharmacological actions. In the present study, dicyclomine hydrochloride, an antispasmodic drug, was tested for possible antimicrobial property in vitro and in vivo. METHODS: The minimum inhibitory concentration (MIC) of dicyclomine against the bacteria was determined by agar and broth dilution methods in vitro. The antibacterial activity of dicyclomine was confirmed by animal experiments. Toxicity and protective efficacy of the drug were tested in vivo. RESULTS: Dicyclomine inhibited most of the bacterial isolates tested at 25-100 microg/ml concentration, and a few were sensitive even at a lower concentration (10 microg/ml). Dicyclomine was found to be bacteriostatic in nature against Shigella dysenteriae 7, and bactericidal against S. aureus NCTC 6571, 8530, and 8531. When administered to Swiss white mice at doses of 30 and 60 microg/mouse, dicyclomine protected the animals challenged with 50 MLD of Salmonella typhimurium NCTC 74. INTERPRETATION & CONCLUSION: Dicyclomine showed inhibitory action against several pathogenic bacteria. It also offered significant protection to mice against the bacterial challange. As dicyclomine is in routine therapeutic use, it may be developed as a potent antimicrobial agent in many infections.

Antispasmodic effects of curcuminoids on isolated guinea-pig ileum and rat uterus.

Curcuminoids, a yellow constituent isolated from Curcuma longa Linn. rhizomes was studied for its antispasmodic activity in isolated guinea-pig ileum and rat uterus. Curcuminoids at the concentration of 12 microg/ml significantly inhibited the ileum pre-contracted with acetylcholine (ACh) 5 x 10(-7) M and histamine 5 x 10(-7) M. (Force of contraction was 62.84 +/- 4.66% and 75.60 +/- 4.66% respectively) and the effects were prominently observed when the concentration of curcuminoids was increased to 36 microg/ml. (Force of contraction was 44.93 +/- 4.33% and 42.79 +/- 1.98%). In potassium depolarizing Tyrode solution, curcuminoids 4 microg/ml and 20 microg/ml reduced the contraction induced by calcium chloride (CaCl2) 1.8 mM. (The contraction was 63.31 +/- 1.80% and 36.87 +/- 3.25%). In rat uterus smooth muscle preparation, curcuminoids 8 microg/ml and 16 microg/ml significantly reduced force and frequency of contraction induced by oxytocin 1 x 10(-2) IU/ml. Curcuminoids 8 microg/ml produced 54.68 +/- 3.34 per cent force of contraction and 79.09 +/- 2.29 per cent frequency of contraction. Curcuminoids 16 microg/ml caused more relaxation of rat uterus smooth muscle. (Force of contraction was 43.38 +/- 3.56%, frequency of contraction was 49.96 +/- 5.20%). Curcuminoids 8 and 16 microg/ml significantly reduced force of contraction induced by KCl 50 mM. (Force of contraction was 54.10 +/- 4.92% and 36.60 +/- 2.99%). The results obtained from this study concluded that curcuminoids produced a smooth muscle, relaxation effect on isolated guinea-pig ileum and rat uterus by receptor-dependent and independent mechanism.

Short and long term effects of 1 percent atropine drops on tear production in mixed breed dogs

Concebeu-se estudarem os efeitos do colírio de sulfato de atropina a 1 por cento sobre a produçäo lacrimal em cäes, por existirem referências sobre sua diminuiçäo, em animais susceptíveis, tratados cronicamente com a droga, embora näo seja consenso entre os autores a possibilidade de induçäo de Ceratoconjuntivite Seca (CCS) nestes pacientes. Neste contexto, procurou-se investigar a atropina quanto a estas intercorrências em cäes sem raça definida que säo pouco ou nada susceptíveis à CCS. Para tanto, foram empregados 20 animais da espécie canina, sem raça definida, machos, adultos e sadios. A lacrimogênese foi avaliada através do teste da lágrima de Schirmer do tipo I. O experimento foi composto por três fases, denominadas pré-atropínica e pós-atropínica. Nas fases pré e pós-atropínica, realizou-se única mensuraçäo diária do parâmetro, durante 14 e 30 dias, respectivamente, näo ocorrendo aplicaçäo do medicamento. Na fase pré-atropínica, pôde-se estabelecer como basal o valor de 20,26 mm/minuto, referente à produçäo lacrimal. A fase atropínica foi dividida em 4 tempos, sendo a primeira mensuraçäo anterior à instilaçäo do fármaco e as demais, posteriores, a intervalos de 1 hora, num total de 3 aferiçöes. Os resultados obtidos permitem afirmar que o emprego tópico do sulfato de atropina a 1 por cento, em cäes, acarretou diminuiçäo na produçäo da lágrima, com tendência à normalizaçäo após a interrupçäo do tratamento.

Influence of intragastric perfusion of aqueous spice extracts on acid secretion in anesthetized albino rats.

BACKGROUND: The effect of spices on gastric acid secretion is variable. Their mechanism of action is also not well established. AIM: To study the effect of spices on gastric acid secretion in anesthetized rats. METHODS: Aqueous extracts (10% w/v) of red pepper (Capsicum annuum), fennel (Foeniculum vulgare), omum/ajwan (Carum copticum), cardamom (Elettaria cardamomum), black pepper (Piper nigrum), cumin (Cuminum cyminum) and coriander (Coriandrum sativum) were prepared. The stomach of pentobarbitone-anesthetized rats was perfused at 0.15 mL/min with aqueous extracts of spice or acetylcholine (1 microgram/mL or 10 micrograms/mL solutions, in 40 min blocks, twice in each experiment bracketed by saline perfusions. The acid content in the samples was estimated by titration with 0.1N NaOH with phenolphthalein as indicator. Atropine 1 microgram/mL was added to the perfusion fluid in 28 experiments. In 32, acute gastric mucosal injury was induced by leaving aspirin 125 mg/Kg in the stomach for 2 h before perfusion. RESULTS: All the spices tested increased acid secretion in the following declining order: red pepper, fennel, omum, cardamom, black pepper, cumin, coriander. Red pepper increased acid secretion (mean [SEM] 0.93 [0.16] mL 0.1N HCl) to about 7 times the basal secretion (0.14 [0.05]; p < 0.005). The increase in acid secretion by the other spices was as follows: fennel 0.42 (0.11) mL 0.1 N HCl from basal secretion (0.12 [0.03]) (p < 0.02); omum 0.33 (0.05) from 0.09 (0.02) (p < 0.01); cardamom 0.28 (0.04) from 0.10 (0.03) (p < 0.005); black pepper 0.19 (0.03) from 0.04 (0.01) (p < 0.005); cumin 0.12 (0.02) from 0.08 (0.01) (p < 0.05); coriander 0.18 (0.03) from 0.09 (0.02) (p < 0.005). Atropine abolished the acid secretion induced by acetylcholine and significantly reduced acid induction by red pepper, omum and coriander, but not that by fennel. In experiments with aspirin-induced mucosal injury the basal acid secretion was low; acid secretion by red pepper and fennel was reduced significantly, but not that by acetylcholine. Cumin and coriander increased acid secretion in injured stomachs. CONCLUSION: The spices tested increased gastric acid secretion, in some by a cholinergic mechanism but by other mechanism(s) as well. Red pepper produced maximum increase in acid secretion, but this was significantly reduced in injured stomachs. Cumin and coriander increased gastric secretion in injured stomachs.

Pharmacological effects of essential oils of plants of the Northeast of Brazil

The authors have reviewed the pharmacological studies done with essential oils obtained in the state of Ceará, in Northeast of Brazil, from 25 species of aromatic plants, some of which are native to the phytogeographic semiarid region characteristic of the Northeast, the "caatingas". These studies have dealt with the effect of these oils on muscle contraction and with their antisopasmodic, analgesic, antiinflammatory, anticonvulsant and antibacterial activity. The essential oils of the medicinal species have shown activity coherent with the use of these plants in folk medicine. The review is aimed primarily at summarizing the information relevant for a critical evaluation of the perspectives and potential of these oils as pharmacological and therapeutic agents.

Antispasmodic action of propinox on the isolated human gallbladder: possible mechanism of action

Propinox is an antispasmodic drug frequently used in the treatment of disorders of the gastrointestinal tract, the uterus and the galbladder, but little is known about its relaxing activity in gallbladder tissue. The main objective of this study was to determine the antispasmodic activity of propinox, compared to other antispasmodics, in the gallblader and to assess its binding affinity to receptor sites which may be involved in its mechanism of action. Antispasmodic activity of propinox, (-) scopolamine-n-butyl bromide, atropine and verapamil was determined in human gallbladders to reduce the risk of interspecies variability. Inhibitory activities (ED50) of carbachol-induced contraction were: atropine 5.03x10(-8) M>propinox 1.25x10(-7) M> verapamil 6.63x10(-6)M> (-) scopolamine-n-butyl1 bromide 5.4x10(-5) M. pD'2 for propinox was 6.94, indicating non competitive inhibition of carbachol action. Radioligand binding studies were performed to determine if the antisplasmodic action of the drug involved binding to muscarinic receptors or calciumatagonist sites. The inhibition constant (Ki) of proponix for muscarinic receptors of guinea pig ileum smoth muscle, which contains a mixed M2-M3 receptor population, was 1.6x10(-6) M. Ki for brain muscarinic receptors (M1) was 1.0x10(-4) M, for cardiac receptors (M1) was 1.0x10(-4)M, for receptors (M2) 1.2x10(-6)M and from salivary gland receptors (M3) 1.5x10(-6)M. For binding to the dihidropiridine calcium antagonist binding sites, Ki were: 4.9x10(-5)M for propinox and 2.2x10(-7)M for verapamil. For the phenylakylamine binding sites Ki were: 5.0x10(-6)M for propinox and 3.5x10(-8)M for verapamil. For the benzothiacepine binding sites, Ki for propinox was 5.2x10(-6)M. The following may be concluded: 1- The antispasmodic activity of propinox in isolated human galbladder was was comparatively less potent than of atropine and more potent than those verapamil and (-) scopolamine-n-butyl bromide. 2- Propinox showed binding to muscarinic and calcium receptors that can be related to its antisplasmodic activity; suggesting that the drug is an antispasmodic with anticholinergic and musculotropic activity. 3.- The dual mechanism of action, anticholinergic and calcium-blocking, would induce synergism of pharmacodynamic effects and minimize adverse events of pure antimuscarinic drugs or calcium antagonists.

Botanical, chemical and pharmacological investigation on Cissampelos species from Paraíba (Brazil)

In our continuing search for biologically active compounds of local medicinal flora, we have investigated the genus Cissampelos (Meninspermaceae) whose species are used in ethnomedicine mainly for treatment of the diseases of the respiratory system. From the three species found in Paraiba: C. sympodialis, C. glaberrima and C. ovalifolia, only the first one was analyzed more extensively due to its greater availability and the high yield of warifteine, a bisbenzyltetrahydroisoquinoline alkaloid isolated from it. The water soluble fractions of the ethanolic extracts of the root, leaf and warifteine obtained from either of the fractions caused nonspecific smooth muscle relaxation in tissues such as the guinea pig trachea. The leaf fraction also showed bronchodilatory activity in whole animal experiments and inhibited human neutrophil degranulation induced by the peptide formyl-methionine-leucine-proline. The mechanism of action of the fraction involves on increase in intracellular cyclic adenosine monophosphate levels possibly as a result of the inhibition of nucleotide phosphodiesterase enzymes. The antiasthmatic use of the plant Cissampelos sympodialis may have scientific justification.

The plants of the genus Phyllanthus as a potential source of new drugs

The plants of the genus Phyllanthus (Euphorbiaceae) comprise about 550 to 750 species which are widely distributed in most tropical and subtropical countries. About 200 species are believed to occur in the Americas, mainly in the Caribbean and Brazil. The plants of the genus Phyllanthus have long been used in folk medicine to treat, among others, kidney and urinary bladder disorders, intestinal infections, diabetes and hepatitis B. In recent years, substantial progress in chemical and pharmacological studies, and a few clinical studies of some Phyllanthus species, were made. This review discusses the current knowledge gained by the in vitro and in vivo pharmacological and biochemical studies performed with the extracts and the main active constituents isolated from different species of plants of the genus Phyllanthus. Data available in the literature strongly support the idea that the extract and some constituents isolated from these plants, including flavanoids, tannins, alkaloids, coumarins, lignans and terpenes, account for their reported antinociceptive, anti-inflammatory, antiviral, antispasmodic and antiallergic properties. In addition, some of these compounds were found to interact with most key enzymes, such as aldose reductase, angiotensin converting enzyme, mitochondrial ATPase, both cyclo- and lipooxygenases, phospholipase A2, tyrosine kinase, reverse transcriptase, and phosphodiesterases. The complex mechanism of action of such compounds could explain, at least in part, the wide therapeutic use of the plants of the genus Phyllanthus in folk medicine. Thus, the plants of the genus Phyllanthus present potential therapeutic interest as a source of new drugs.

Uso del agente espamolitico otilonio bromuro (spamonen) en endoscopia digestiva: estudio prospectivo en 63 pacientes / Use of spasmolytic agent otilonium bromide in digestive endoscopy: a prospective study in 63 patients

El otilonio bromuro es un antagonista del calcio con un efecto miolítico directo, el cual está indicado en estados espásticos y disguinesias funcionales del aparato gastroentérico (sindrome del intestino irritable) y como premedicación para procedimientos endoscópicos gastrointestinales. El presente estudio evaluó el otilonio bromuro 40 mg PO la noche anterior y 40 mg PO la mañana de 49 fibroscopías bajas en 63 pacientes, para determinar la presencia o ausencia de peristalsis y relajación del píloro. No se observaron efectos colaterales debido a la medicación. En 46 (93.8 por ciento) endoscopías altas se observó marcada relajación del tracto gastrointestinal y del píloro. En 13 (92.8 por ciento) endoscopías bajas también se observó marcada relajación del tracto colónico. Todos los pacientes toleraron bien las endoscopías. El otilonio bromuro fue útil como premedicación para facilitar las exploraciones endoscópicas altas y bajas, debido a su efecto espasmolítico.

Effect of oral administration of Terminalia chebula on gastric emptying: an experimental study.

Terminalia chebula is a commonly advocated agent in Ayurveda for improving gastrointestinal motility. Charles Foster rats (150-200 gms of either sex) were divided into four groups as follows--Group 1 (n = 15) normal animals; Group II (n = 6) rats administered metoclopramide (1.35 mg/kg); Group III (n = 8) rats given atropine (0.45 mg/kg). These agents were injected intramuscularly, 30 mins before the experiment. Rats from Group IV (n = 8) were administered Terminalia chebula (100 mg/kg/day for 15 days orally). Metoclopramide and atropine have established prokinetic and antikinetic activities respectively and are therefore included for comparison. All rats were then given a test meal of methyl cellulose (1.5%) mixed with phenol red (50 mg/100 ml) orally and gastric emptying was measured 20 mins later. Gastric emptying of normal rats (Group I) was found to be 51.6 +/- 7.79%. Metoclopramide significantly increased the gastric emptying (76.33 +/- 12.37%; p < 0.01) and atropine inhibited the motility (% gastric emptying being 7.26 +/- 19.76%; p < 0.01). Terminalia chebula was found to increase the percent gastric emptying (86.57 +/- 6.65%; p < 0.01). Thus from this study it appears that Terminalia chebula can serve as an useful alternative to prokinetic drugs available today.

Drogas parassimpaticolíticas na terapêutica ocular / Parasympatholytics drugs in ocular therapeutic

Os autores fazem uma revisao dos aspectos farmacológicos de drogas anticolinérgicas na terapia ocular. É demonstrado o fármaco de escolha para algumas situaçoes práticas dentro da clínica oftalmológica e também se procede a um estudo comparativo entre essas mesmas drogas. Com isso, procura-se trazer ao clínico uma visao prática do uso desses fármacos, o que, certamente, contribuirá para esclarecer alguma situaçoes do dia-a-dia da práxis médica.

Parasympatholytic activity of psychoactive drugs in rat brain mitochondria.

Chlorpromazine, imipramine and amphetamine at a concentration of 0.66, 1.33 and 13.3 x 10(4) M in vitro inhibited acetyl cholinesterase activity by 16, 23 and 31% respectively in rat brain mitochondria. No change in enzyme activity was induced by these drugs in vivo. There is little cholinergic facilitation through acetylcholinesterase inhibition in the presence of psychoactive drugs.