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At least 1,261 records · Page 70Linked to original sources
PubMed2004

Cistus incanus and Cistus monspeliensis inhibit the contractile response in isolated rat smooth muscle.

The lyophilized aqueous extracts from Cistus incanus L. (CI) and Cistus monspeliensis L. (CM) collected in Sicily were studied in order to evaluate their myorelaxant activity by using isolated smooth muscle of rat ileum and rat aorta. Both CI and CM extracts concentration-dependently inhibited the contractile response to acetylcholine (ACh), phenylephrine (PE) and to 100 mM KCl. The concentration-contraction curves to ACh in ileum and to PE in aorta, were displaced to the right by Cistus extracts in a non-competitive manner, with a depression of the maximum contractile response. The EC50 (microg/ml) of CM and CI were: ileum/KCl, CM 457+/-99, CI 681+/-80; ileum/ACh 100 microM, CM 297+/-66, CI 335+/-41; aorta/KCl, CM 360+/-21, CI 843+/-36; and aorta/PE 10 microM, CM 287+/-33, CI 451+/-58. The two extracts resulted almost equi-active in ileum, whereas CM was more active than CI in aorta. These data indicate that Cistus extracts act as spasmolytic on intestinal and vascular smooth muscle. The antagonism they exert on ACh-, PE- and KCl-evoked contractions seems to be functional, because it is not specifically directed toward any particular receptor; furthermore, a calcium-antagonist activity seems unlikely, since the extracts are capable of completely block the contractile response to agonists.

Acetylcholine↗
PubMed2004

Pharmacological basis for the gut stimulatory activity of Raphanus sativus leaves.

The crude extract of Raphanus sativus leaves (Rl.Cr) showed a dose-dependent (0.03-5.0 mg/ml) spasmogenicity in guinea-pig ileum and colon. The effect was insensitive to atropine pre-treatment but was completely abolished by pyrilamine indicating involvement of histaminergic (H(1)) receptors. The contractile effect at high doses (3.0-5.0mg/ml) was followed by relaxation. Rl.Cr also enhanced the transit of charcoal meal in mice at 30-100 mg/kg. The petroleum spirit, chloroform and aqueous fractions all showed histaminergic activity in ileum; aqueous fraction being more potent. The study shows the presence of a histaminergic component(s) along with a weak spasmolytic factor thus providing sound mechanistic basis for the traditional use of the plant in constipation.

Animals↗
PubMed2005

Anti-diabetic effect on alloxanized and normoglycemic rats and some pharmacological evaluations of Tournefortia hartwegiana.

The purpose of the present investigation was to assess the pharmacological properties of Tournefortia hartwegiana Steud (Boraginaceae), used in traditional medicine for the treatment of diabetes, diarrhea and kidney pain in Morelos, Mexico. Administration of methanol extract from aerial parts of Tournefortia hartwegiana (310 mg/kg body weight/day) for 10 days, to normoglycemic and alloxan-induced diabetic rats, significantly lowered their blood glucose levels (37 and 36%, respectively, p<0.05). The anti-diabetic and hypoglycemic activities due to the MeOH extract were similar to those produced by metformin at 120 mg/kg (positive control, p<0.05). In contrast, the hexane, dichloromethane and MeOH extracts from the same species showed no significant spasmolytic effect and did not have activity in antibacterial and Artemia salina toxicity bioassays.

Alloxan↗
PubMed2004

Characterization of a CCAAT-enhancer element of trefoil factor family 2 (TFF2) promoter in MCF-7 cells.

Trefoil factors family 2 (TFF2), also known as spasmolytic polypeptide, is primarily expressed in the mucus neck cells of gastrointestinal tracts. It has been proposed that TFF2 plays an important physiological role in protection, repair, and healing of gastrointestinal mucosa. To investigate the cis-acting regulatory element that control TFF2 tissue-specific expression, we studied the basal TFF2 promoter activity through transient transfection in several human cancer cell lines. Expression of TFF2 was found to be significantly greater in human breast cancer MCF-7 cells compared to other cancer cells. Results from TFF2 promoter luciferase reporter constructs revealed that the basal level of TFF2 promoter activity was overall more than two-fold higher in MCF-7 cells compared to that of other cell lines examined. Using EMSA assays and site-directed mutagenesis, we identified a cell line-specific transcriptional regulation element located in the TFF2 promoter 5'-flank sequence at -32/-27, and which contains a CCAAT/enhance binding proteins (C/EBPs) consensus-binding site. Mutation of this consensus site reduced the basal promoter activity by more than 50% in MCF-7 cells but had no effect in human gastric cancer cells. In conclusion, we have identified a CCAAT sequence as a cell line-specific cis-acting regulatory element that may contribute to the high level expression of TFF2 in MCF-7 cells. These results also suggest the possibility that TFF2 could play a role in mammary gland tumorigenesis.

Base Sequence↗
PubMed2005

Gastrointestinal clinical pharmacology of peppermint oil.

In nine studies, 269 healthy subjects or patients underwent exposure to peppermint oil (PO) either by topical intraluminal (stomach or colon) or oral administration by single doses or 2 weeks treatment (n = 19). Methods used to detect effects were oro-cecal transit time by hydrogen expiration, total gastrointestinal transit time by carmine red method, gastric emptying time by radiolabelled test meal or sonography, direct observation of colonic motility or indirect recording through pressure changes or relieve of colonic spasms during barium enema examination. The dose range covered in single dose studies is 0.1-0.24ml of PO/subject. With one exception, which show an unexplained potentiation of neostigmine stimulated colon activity, all other studies result in effects, indicating a substantial spasmolytic effect of PO of the smooth muscles of the gastrointestinal tract. Pharmacokinetic studies reveal that fractionated urinary recovery of menthol is dependent on the kind of formulation used for the application of PO. Optimal pH triggered enteric coated formulations start releasing PO in the small intestine extending release over 10-12 h thus providing PO to the target organ in irritable bowel syndrome, i.e. the colon. The hypothesis is supported by anecdotal observations in patients with achlorhydria or ileostoma, respectively.

Administration, Oral↗
PubMed2006

Functional dyspepsia--a multicausal disease and its therapy.

Functional dyspepsia is a common chronic disorder with non-specific upper abdominal symptoms which can not be explained by organic or biochemical abnormalities. The dyspeptic symptoms are very compromising and bothersome and result in a substantial reduction of quality of life. The substantial direct and indirect medical and economical costs induce a high socioeconomic interest in the pathogenesis and the treatment options of this disease. Over the past 30 years several theories about the etiology of the symptoms in functional dyspepsia patients have been put forward. These include disorders of gastrointestinal motility, acid secretion, visceral hypersensitivity, adaptation and accommodation, Hp-infection, mucosal inflammation and finally genetic predisposition. There is increasing evidence that functional dyspepsia is a multi-causal disorder, which leads to altered processing of afferent information from the gastrointestinal tract to the CNS. Autonomic hypersensitivity and altered central processing could be a common phenomenon whereas motility changes, inflammation or altered secretion could increase neural afferent inputs. Treatment of this complex disorder could and should involve these different levels of symptom generation. Thus different approaches with anti-secretory, spasmolytic, prokinetic and anti-inflammatory effects and most preferably reduction of visceral hypersensitivity seem logical. This could explain the variety of drugs which show a positive symptomatic response. This could also offer the conclusion, whether a combination of these drugs could be clinically superior which remains to be proven. And this could offer a logical approach for the use of substances with a multi-target action, e.g. STW 5.

Diagnosis, Differential↗
PubMed2006

Effect of Thymol on the spontaneous contractile activity of the smooth muscles.

Effects of Thymol on the spontaneous contractile activity (SCA) have been found in in vitro experiments with circular smooth-muscle strips (SMAs) from guinea pig stomach and vena portae. Thymol was found to possess an agonistic effect on the alpha(1)-, alpha(2)- and beta-adrenergic receptors. Its spasmolytic effect is registered at doses higher than 10(-6)M. Thymol in a dose of 10(-4)M inhibits 100% the SCA of the SMAs and reduces the excitatory effect of 10(-5)M ACH to 35%. It is assumed that Thymol has an analgesic effect through its action on the alpha(2)-adrenergic receptors of the nerve cells. By influencing the beta-adrenergic receptors in the adipose cells, it is possible to induce increased synthesis of fatty acids and glycerol, which is a prerequisite for increased heat release.

Adrenergic Agonists↗
PubMed2005

Does dipyrone have any effect on respiratory function in COPD patients?

OBJECTIVE: Dipyrone (Novalgin) is an effective analgesic, antipyretic agent also with spasmolytic effects on various types of smooth muscles. It has recently been reported that dipyrone relaxes tracheal smooth muscle of guinea pig. In this present study, we aimed to investigate whether this and previously reported in vitro results have any consequences on the respiratory function of normal healthy volunteers and chronic obstructive pulmonary disease (COPD) patients. METHODS: In this one-centered, non-randomized, non-comparative, open labelled study, 15 normal healthy volunteers and 15 stable COPD patients, with partially reversible bronchospasm, diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria were enrolled in the study at the time they had any indication of dipyrone use. The spirometric tests were performed by a portable notebook and Medikro Spiro2000 spirometry programme-software 1.6 version, before 30, 60, 90, and 120 min after 20 mg/kg of orally dipyrone intake. Groups were compared with the General Linear Model Repeated Measures analysis of variance. RESULTS: None of the spirometric parameters evaluated showed any significant differences when compared with the baseline values in both groups. CONCLUSION: While dipyrone had no bronchodilator effects on either COPD patients or normal volunteers, it also did not impair the spirometric parameters. Since COPD is a disease characterized by a progressive and largely irreversible airflow limitation, dipyrone has no observable bronchodilator effect. However, since dipyrone does not impair the pulmonary function, it can be used safely in COPD patients when there is an indication.

Adult↗
PubMed2002

Autoinduction of the trefoil factor 2 (TFF2) promoter requires an upstream cis-acting element.

Trefoil factor 2 (TFF2)/spasmolytic polypeptide (SP) is a highly stable peptide which is abundantly expressed and secreted by mucous cells of the stomach and which functions in gastric cytoprotection. Previous studies from our group have shown that TFF2 is an immediate early gene capable of regulating its own expression through activation of the TFF2 promoter. We therefore aimed to investigate the cis-acting elements mediating this response in AGS cells transfected with TFF2 promoter-reporter gene constructs, using a TFF2-expression system resembling physiologic paracrine conditions. TFF2 peptide expression was achieved through stable transfection of AGS cells with a TFF2-expression construct. Stimulation of transiently transfected cells with this TFF2-containing conditioned media resulted in a significant increase in TFF2 promoter activity. Promoter stimulation was blocked by an anti-TFF2 antibody, indicating that it was mediated specifically by TFF2. Deletion analysis of the TFF2 promoter led to the identification of a specific response element located between -191 and -174 upstream of the transcriptional initiation site. This region of the promoter, which was designated SPRE (for spasmolytic polypeptide response element), was sufficient to confer responsiveness in a heterologous promoter system. Mutational analysis and electrophoretic mobility shift assays (EMSA) showed that a GAG motif was responsible for mediating promoter activation in response to TFF2 stimulation. Since auto- and cross-induction of TFF2 promoter is likely to be a means of rapid amplification of TFF2 expression in the critical first minutes following mucosal injury, these results should lead to insight into the molecular events initiating epithelial restitution and healing.

Base Sequence↗
PubMed1986

Synthesis and biological properties of antiparallel and parallel dimers of alpha-human atrial natriuretic peptide.

To obtain antiparallel and parallel dimers of alpha-human atrial natriuretic peptide (alpha-hANP), two fully protected peptides I and II having the same amino acid sequence as alpha-hANP with different protective groups at the cysteinyl residues were synthesized, the former having Acm and Npys and the latter MeBzl and Acm. Equivalent amounts of peptides I and II were mixed and subjected to HF deprotection. Next, the first disulfide bond was linked between the remaining Npys group in I and the liberated SH group in II to form a monodisulfide dimer. The second disulfide bond was formed within the newly formed dimer between the remaining Acm groups by treatment with iodine, giving an antiparallel dimer. The parallel dimer of alpha-hANP was synthesized similarly starting from the protected peptide II. These dimers could be clearly segregated on HPLC. The retention time on HPLC of the antiparallel dimer was identical with that of natural beta-hANP. Both dimers showed biological activities as high as one third to one sixth of alpha-hANP in smooth muscle spasmolytic activity, and almost the same level of natriuretic activity as alpha-hANP at a high dose (10 nmol/kg) but about one fifth the activity at a low dose (1 nmol/kg). In these assay systems, the antiparallel dimer showed a slower onset and a tendency of longer duration than alpha-hANP.

Amino Acid Sequence↗
PubMed2000

Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla.

Dried flowers of Matricaria chamomilla L. are largely used to provide sedative as well as spasmolytic effects. In the present study, we examined in particular the pharmacological property of a fraction isolated from a methanolic extract of M. chamomilla, which was identified by HPLC-MS-MS analysis as apigenin. By radioreceptor binding assays, we demonstrated the ability of the flavone to displace a specific radioligand, [(3)H]Ro 15-1788, from the central benzodiazepine binding site. Electrophysiological studies performed on cultured cerebellar granule cells showed that apigenin reduced GABA (gamma-aminobutyric acid)-activated Cl(-) currents in a dose-dependent fashion. The effect was blocked by co-application of Ro 15-1788, a specific benzodiazepine receptor antagonist. Accordingly, apigenin reduced the latency in the onset of picrotoxin-induced convulsions. Moreover, apigenin injected i.p. in rats reduced locomotor activity, but did not demonstrate anxiolytic, myorelaxant, or anticonvulsant activities. The present results seem to suggest that the inhibitory activity of apigenin on locomotor behaviour in rats cannot be ascribed to an interaction with GABA(A)-benzodiazepine receptor but to other neurotransmission systems, since it is not blocked by Ro 15-1788.

Animals↗
PubMed2003

The antioxidant activity of caroverine.

Caroverine, 1-(2-diethylaminoethyl)-3-(p-methoxy benzyl)-1,2-dihydro-2-quinoxalin-2-on-hydrochloride, is a class B calcium-channel-blocker and antiglutamatergic agent with significant effects on the brain function. Caroverine exhibits competitive AMPA antagonism, and at higher concentrations, noncompetitive NMDA antagonism. In clinical practice caroverine is used as a spasmolytic and otoneuroprotective agent. Since reactive oxygen species are supposed to be involved in the pathogenesis of inner ear diseases in which caroverine shows beneficial effects, the present study aimed to investigate the antioxidant properties of caroverine. Lipid peroxidation of liposomal membranes was suppressed in the presence of caroverine. In order to understand the mechanism of this antioxidant action of caroverine, we determined the rate constants both for a possible reaction with superoxide (O(2)(.-)) radicals from xanthine/xanthine oxidase and for a possible reaction with hydroxyl (.OH) radicals in Fenton system. Using a defined chemical reaction model O(2)(.-) scavenging was found to occur at a rather low rate constant only (3 x 10(2)M(-1)s(-1)). Thus, a reaction of caroverine with O(2)(.-) radicals is of marginal significance. In contrast, the reaction of caroverine with .OH radicals occurs at an extremely high rate constant (k=1.9 x 10(10)M(-1)s(-1)). The strong antioxidant activity of caroverine is therefore based both on the partial prevention and highly active scavenging of hydroxyl radicals.

Analysis of Variance↗
PubMed2001

The distribution of major lymphocyte subsets in cord blood is associated with its pH.

OBJECTIVES: To assess in venous cord blood the distribution of major lymphocyte subsets according to pH and medications used during labor. DESIGN AND METHODS: Venous cord blood was sampled immediately after labor from 70 newborns (35 males and 35 females) delivered vaginally. Lymphocytes were immunophenotyped by flow cytometry and pH was measured using the AVL 900 automated blood gas analysis system. Data on birth weight, gestational age at delivery, length of labor, presence of stained amniotic fluid, medications used during labor, maternal risk factors, age and parity were collected. RESULTS: The percentage of T lymphocytes decreased while the percentage of NK lymphocytes increased with decreasing pH over the whole range of pH values. The proportions of T and NK lymphocytes were associated with the administration of neuroplegics, spasmolytics or dihydroergotoxin in the first stage of labor. CONCLUSIONS: Cord blood pH and labor-associated variables should be taken into account to adequately interpret the profile of major lymphocyte subsets as a marker of the effect of different prenatal factors on the immune system of neonates.

Adolescent↗
PubMed1995

Use of antispasmodic drugs in double contrast barium enema examination: glucagon or buscopan?

PURPOSE: To compare the spasmolytic effect of glucagon and buscopan in double contrast barium enema examination. PATIENTS AND METHODS: Three hundred and twenty-four consecutive patients referred for double contrast barium enema examination were randomly allocated to receive an intravenous injection of either 1 mg of glucagon, 20 mg of buscopan or physiological saline. The transit of the barium column from rectum to caecum, the quality of the radiographs and side effects were assessed blindly without knowledge of the injected drug. RESULTS: Antispasmodic drugs (glucagon or buscopan) resulted in better transit of the barium column to the caecum compared to placebo (Mann-Whitney: P < 0.05), but no differences occurred between glucagon and buscopan (Mann-Whitney: P > 0.05). Buscopan produced better distension of the rectosigmoid than glucagon or placebo (P < 0.05). Of 109 patients who received buscopan five complained of blurred vision afterwards. CONCLUSION: Because buscopan is less expensive and more effective in distending the colon than glucagon, it is preferred for the routine double contrast examination. However, patients should be warned about the possibility of temporary visual impairment.

Adult↗
PubMed2000

Possible site of action of TAK-637, a tachykinin NK(1) receptor antagonist, on the micturition reflex in guinea pigs.

TAK-637((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1,7]naphthyridine-6,13-dione) is a novel tachykinin NK(1) receptor antagonist that has been shown to inhibit the micturition reflex in guinea pigs. The aim of this study was to clarify its mechanism of action in guinea pigs. TAK-637 inhibited the spinal vesico-vesical reflex induced by electrical stimulation of the proximal cut end of the pelvic nerve in spinal animals, but not bladder contractions induced by electrical stimulation of the distal cut end of the nerve. Furthermore, TAK-637 had no effect on carbachol- or electrical field stimulation-induced contractions of isolated bladder muscle strips in an organ bath, whereas drugs used for abnormally frequent micturition inhibited both contractions. These results suggest that TAK-637 inhibits the micturition reflex by acting, at least in part, on the spinal cord, and its mechanism of action clearly differs from those of antimuscarinics or spasmolytics.

Animals↗
PubMed2001

Pharmacological actions of AH-9700 on micturition reflex in anesthetized rats.

In radioligand binding assays, AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl]pyrrolidine fumarate) had high affinity for sigma receptors and moderate affinity for muscarinic receptors. The affinity of AH-9700 for sigma(1) receptors was significantly reduced in the presence of 5'-guanylyl-imidodiphosphate (GppNHp). In isolated bladder strips of rats, AH-9700 inhibited carbachol-induced contractions. In anesthetized rats, i.v. administration of AH-9700 and typical sigma receptor ligands, (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), but not oxybutynin, dose-dependently inhibited rhythmic isovolumetric reflex bladder contractions. AH-9700 and oxybutynin suppressed the amplitude of rhythmic bladder contractions. On the other hand, at doses lower than used i.v., the i.c.v. administration of AH-9700 or the sigma receptor ligands inhibited rhythmic bladder contractions without suppressing the amplitude. This inhibitory effect of AH-9700 was markedly reduced by pretreatment with i.c.v. pertussis toxin. These results suggest that AH-9700 exerts a marked anti-micturition reflex effect through central sigma receptors possibly related to pertussis toxin-sensitive Gi/o-proteins and a moderate spasmolytic effect based on its peripheral anti-muscarinic activity.

Anesthesia↗
PubMed2001

New metal complexes of 4-methyl-7-hydroxycoumarin sodium salt and their pharmacological activity.

Complexes of copper (II), zinc (II), nickel (II), cobalt (II) and iron (III) with 4-methyl-7-hydroxycoumarin sodium salt (Mendiaxon, Hymecromone) were synthesized by mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1H NMR spectroscopy and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. Thermal analysis of the complexes indicate the formation of compounds which correspond to the compositions Met(HL)2 x nH2O, where Met = Cu, Zn, Ni, Co; n = 2, 3 or 4 and Fe(HL)3 x 5H2O. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity.

Administration, Oral↗
PubMed2002

Synthesis and pharmacological properties of benzisothiazole/benzimidazole derivatives with acidic groups.

The synthesis and the pharmacological evaluation of benzisothiazole and benzimidazole tetrazolyl- and carboxyl- derivatives 1-6 are described. Structural modification was aimed at investigating the influence of two isosteric substituents (tetrazolyl- and carboxyl-) on the title benzofused heterocycles. The antiphlogistic, antipyretic and analgesic activities have been investigated in in vivo experimental models. Additional investigations have been performed in vitro to study the antiplatelet and spasmolytic activity of the compounds synthetized. All the compounds produced peripheral analgesic effects, but were less effective in hot plate test. The tetrazole and the carboxylic benzisothiazole derivatives 2 and 3 proved to be the most effective drugs within the series, exhibiting maximal inhibition of writhes with a potency 3-fold higher than that of acetaminophen. Only compound 5 provided indication for a central analgesic activity since it was active in hot plate test although with a low potency. The findings obtained in these in vivo and in vitro studies indicate that these compounds do not share the same mechanism of action of acetaminophen. All of the compounds under study present lower acute toxicity than acetaminophen when orally administered in mice.

Acetaminophen↗