Supplementation With Spirulina platensis Improves Tracheal Reactivity in Wistar Rats by Modulating Inflammation and Oxidative Stress.

Spirulina platensis has shown effectiveness in the treatment of allergic rhinitis in rats, but its action in tracheal reactivity or on markers of relaxation and antioxidant profile has not yet been possible to determine. In this paper, the animals were divided into the groups healthy (SG) and supplemented with S. platensis at doses of 50 (SG50), 150 (SG150), and 500 mg/kg (SG500). We also evaluated nitrite levels, lipid peroxidation, and antioxidant activity through biochemical analysis. For contractile reactivity, only SG500 (pEC50 = 5.2 ± 0.06 showed reduction in carbachol contractile potency. Indomethacin caused a higher contractile response to carbachol in SG150 and SG500. For relaxation, curves for SG150 (pEC50 = 5.0 ± 0.05) and SG500 (pEC50 = 7:3 ± 0:02) were shifted to the left, more so in SG500. We observed an increase in nitrite in the trachea only with supplementation of 500 mg/kg (54.0 ± 8.0 µM), also when compared to SG50 (37.0 ± 10.0 µM) and SG150 (38.0 ± 7.0 µM). We observed a decrease in lipid peroxidation in the plasma and an increase in oxidation inhibition for the trachea and lung in SG150 and SG500, suggesting enhanced antioxidant activity. S. platensis (150/500 mg/kg) decreased the contractile response and increased relaxation by increasing antioxidant activity and nitrite levels and modulating the inflammatory response.

Uncovering the Role of Oxidative Imbalance in the Development and Progression of Bronchial Asthma.

Asthma is a chronic inflammatory disease of the airways related to epithelial damage, bronchial hyperresponsiveness to contractile agents, tissue remodeling, and luminal narrowing. Currently, there are many data about the pathophysiology of asthma; however, a new aspect has emerged related to the influence of reactive oxygen and nitrogen species (ROS and RNS) on the origin of this disease. Several studies have shown that an imbalance between the production of ROS and RNS and the antioxidant enzymatic and nonenzymatic systems plays an important role in the pathogenesis of this disease. Considering this aspect, this study is aimed at gathering data from the scientific literature on the role of oxidative distress in the development of inflammatory airway and lung diseases, especially bronchial asthma. For that, articles related to these themes were selected from scientific databases, including human and animal studies. The main findings of this work showed that the respiratory system works as a highly propitious place for the formation of ROS and RNS, especially superoxide anion, hydrogen peroxide, and peroxynitrite, and the epithelial damage is reflected in an important loss of antioxidant defenses that, in turn, culminates in an imbalance and formation of inflammatory and contractile mediators, such as isoprostanes, changes in the activity of protein kinases, and activation of cell proliferation signalling pathways, such as the MAP kinase pathway. Thus, the oxidative imbalance appears as a promising path for future investigations as a therapeutic target for the treatment of asthmatic patients, especially those resistant to currently available therapies.

Virgin Coconut Oil Supplementation Prevents Airway Hyperreactivity of Guinea Pigs with Chronic Allergic Lung Inflammation by Antioxidant Mechanism.

Asthma is a chronic inflammatory disease of the airways characterized by immune cell infiltrates, bronchial hyperresponsiveness, and declining lung function. Thus, the possible effects of virgin coconut oil on a chronic allergic lung inflammation model were evaluated. Morphology of lung and airway tissue exhibited peribronchial inflammatory infiltrate, epithelial hyperplasia, and smooth muscle thickening in guinea pigs submitted to ovalbumin sensitization, which were prevented by virgin coconut oil supplementation. Additionally, in animals with lung inflammation, trachea contracted in response to ovalbumin administration, showed a greater contractile response to carbachol (CCh) and histamine, and these responses were prevented by the virgin coconut oil supplementation. Apocynin, a NADPH oxidase inhibitor, did not reduce the potency of CCh, whereas tempol, a superoxide dismutase mimetic, reduced potency only in nonsensitized animals. Catalase reduced the CCh potency in nonsensitized animals and animals sensitized and treated with coconut oil, indicating the participation of superoxide anion and hydrogen peroxide in the hypercontractility, which was prevented by virgin coconut oil. In the presence of L-NAME, a nitric oxide synthase (NOS) inhibitor, the CCh curve remained unchanged in nonsensitized animals but had increased efficacy and potency in sensitized animals, indicating an inhibition of endothelial NOS but ineffective in inhibiting inducible NOS. In animals sensitized and treated with coconut oil, the CCh curve was not altered, indicating a reduction in the release of NO by inducible NOS. These data were confirmed by peribronchiolar expression analysis of iNOS. The antioxidant capacity was reduced in the lungs of animals with chronic allergic lung inflammation, which was reversed by the coconut oil, and confirmed by analysis of peribronchiolar 8-iso-PGF2α content. Therefore, the virgin coconut oil supplementation reverses peribronchial inflammatory infiltrate, epithelial hyperplasia, smooth muscle thickening, and hypercontractility through oxidative stress and its interactions with the NO pathway.

Metabolomic fingerprinting of Cissampelos sympodialis Eichler leaf extract and correlation with its spasmolytic activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Cissampelos sympodialis Eichler (Menispermaceae) is popularly used in northeastern Brazil for the treatment of respiratory diseases such as bronchitis and asthma. Despite many pre-clinical pharmacological studies, the compounds mediating the anti-asthma activity of polar extracts of Cissampelos sympodialis leaves have not been definitively identified. AIM OF THE STUDY: Aim of the study: The aim of the study was to investigate the correlation between the bioactivity of polar extracts prepared from the leaves of C. sympodialis and the chemical composition using a 1H-NMR-based metabolomics approach. MATERIAL AND METHODS: The metabolic profile of the leaf polar extract during different phenological stages of the plant was investigated using 1H NMR spectroscopy while simultaneously screening for spasmolytic activity using guinea-pig tracheal preparations. The content of the alkaloids previously implicated in the bioactivity of Cissampelos sympodialis was determined by HPLC. RESULTS: PCA analysis of the 1H NMR data discriminated the extracts from different plant phenological stages. The contents of the major alkaloids decrease (from 2 ± 0.32 µg/mL for warifteine and 1 ± 0.14 µg/mL for methylwarifteine) to undetectable levels from 90 (CsL90 extract) and 120 (CsL120) days onwards for warifteine and methylwarifteine, respectively. All six extracts relaxed the trachea pre-contracted with carbachol, but the CsF210 extract was more potent (EC50 = 74.6 ± 7.9 µg/mL) compared to both CsL90 extracts and CsL180 in the presence of functional epithelium. PLS regression analysis of 1H-NMR spectral data demonstrated that the spasmolytic activity was better correlated with signals for flavonol derivatives. CONCLUSIONS: Our data challenge the idea that warifteine and methylwarifteine mediate the spasmolytic activity of the polar extract of C. sympodialis leaves.

Effects of Redox Disturbances on Intestinal Contractile Reactivity in Rats Fed with a Hypercaloric Diet.

Few studies have associated the effects of changes in caloric intake and redox disturbances in the gastrointestinal tract. Therefore, the present study aimed at evaluating the hypercaloric diet consumption influence on the contractile reactivity of intestinal smooth muscle, morphology, and oxidative stress of rat ileum. Wistar rats were randomly divided into groups that received a standard diet and fed with a hypercaloric diet for 8 weeks. Animals were euthanized, and the ileum was isolated to isotonic contraction monitoring. Morphology was evaluated by histological staining and oxidative stress by quantification of malondialdehyde levels and total antioxidant activity. Cumulative concentration-response curves to KCl and carbachol were attenuated in rats fed with a hypercaloric diet compared to those that received a standard diet. In addition, an increase in caloric intake promotes a rise in the thickness of the longitudinal smooth muscle layer of rat ileum and tissue malondialdehyde levels, characterizing lipid peroxidation, as well as a decrease in the antioxidant activity. Thus, it was concluded that the consumption of a hypercaloric diet impairs rat intestinal contractility due to mechanisms involving modifications in the intestinal smooth muscle architecture triggered by redox disturbances.

Aortic Response to Strength Training and Spirulina platensis Dependent on Nitric Oxide and Antioxidants.

Studies have shown that supplementation with Spirulina platensis improves vascular reactivity. However, it is unclear whether in association with strength training this effect can be enhanced. Thus, this study aimed to determine the effects of strength training and S. platensis on the reactivity of the aorta from Wistar rat and the possible mechanisms involved. The animals were supplemented with S. platensis and divided into sedentary (SG, SG50, SG150, and SG500) and trained groups (TG, TG50, TG150, and TG500). Nitrite, malondialdehyde (MDA) and antioxidant activity were determined by biochemical assays. To evaluate vascular response, cumulative concentration-response curves to phenylephrine (PHE) and acetylcholine (ACh) were constructed. L-NAME was used to assess the participation of nitric oxide (NO). It was observed that the PHE contractile potency was reduced in TG50, TG150, and TG500 groups compared to SG50, SG150, and SG500 groups, respectively. However, the presence of L-NAME increased the contractile response in all groups. Strength training potentiated the increase in relaxing activity induced by S. platensis, where the pCE50 values of ACh increased in TG150 and TG500. These responses were accompanied by increased nitrite production, MDA reduction and increased antioxidant activity in the aorta of both TG150 and TG500 groups. Thus, the present study demonstrated that combined with strength training, S. platensis potentiates vascular improvement through the participation of NO and reduction of oxidative stress.

Hypercaloric Diet Establishes Erectile Dysfunction in Rat: Mechanisms Underlying the Endothelial Damage.

Obesity is characterized by an excessive increase in body mass, leading to endothelial damage that may favor the development of erectile dysfunction (ED). ED is defined as the inability to achieve or maintain a penile erection long enough to have a sexual intercourse. In this context, different ED models were developed, however the high price of special animals or the long period to establish the disease has limited studies in this field. Therefore, this study proposed to establish and characterize a novel model of ED in rats associated to a hypercaloric diet consumption. Animals were randomly divided into control group (CG), which received a standard diet, and obese group (OG), fed with a hypercaloric diet during 8 weeks. Rat's erectile function was evaluated in vivo and in vitro. Food and caloric intake of OG were reduced compared to CG, due to an increased diet energy efficiency. However, OG presented an increased body mass, inguinal, retroperitoneal and epididymal adipose tissues, as well as body adiposity index at the end of experimental protocol. In erectile function analysis, there was a decrease in the number and the latency of penile erections in OG. Additionally, the contractile reactivity of corpus cavernosum was increased in OG, favoring penile detumescence and related to a reduced nitric oxide bioavailability and an increased in contractile prostaglandins levels as a consequence of endothelial damage. Moreover, the endothelium-relaxation reactivity of corpus cavernosum was attenuated in OG associated to the oxidative stress. Thus, it was provided a model for advances in sexual dysfunction field and drug discovery for ED treatment.

Acute Aerobic Swimming Exercise Induces Distinct Effects in the Contractile Reactivity of Rat Ileum to KCl and Carbachol.

Aerobic exercise promotes short-term physiological changes in the intestinal smooth muscle associated to the ischemia-reperfusion process; however, few studies have demonstrated its effect on the intestinal contractile function. Thus, this work describes our observations regarding the influence of acute aerobic swimming exercise in the contractile reactivity, oxidative stress, and morphology of rat ileum. Wistar rats were divided into sedentary (SED) and acutely exercised (EX-AC) groups. Animals were acclimated by 10, 10, and 30 min of swimming exercise in intercalated days 1 week before exercise. Then they were submitted to forced swimming for 1 h with a metal of 3% of their body weight attached to their body. Animals were euthanized immediately after the exercise section and the ileum was suspended in organ baths for monitoring isotonic contractions. The analysis of lipid peroxidation was performed in order to determinate the malondialdehyde (MDA) levels as a marker of oxidative stress, and intestinal smooth muscle morphology by histological staining. Cumulative concentration-response curves to KCl were altered in the EX-AC with an increase in both its efficacy and potency (E max = 153.2 ± 2.8%, EC 50 = 1.3 ± 0.1 × 10(-2) M) compared to the SED group (E max = 100%, EC 50 = 1.8 ± 0.1 × 10(-2) M). Interestingly, carbachol had its efficacy and potency reduced in the EX-AC (E max = 67.1 ± 1.4%, EC 50 = 9.8 ± 1.4 × 10(-7) M) compared to the SED group (E max = 100%, EC 50 = 2.0 ± 0.2 × 10(-7) M). The exercise did not alter the MDA levels in the ileum (5.4 ± 0.6 µ mol/mL) in the EX-AC compared to the SED group (8.4 ± 1.7 µ mol/mL). Moreover, neither the circular nor the longitudinal smooth muscle layers thickness were modified by the exercise (66.2 ± 6.0 and 40.2 ± 2.6 µm, respectively), compared to the SED group (61.6 ± 6.4 and 34.8 ± 3.7 µm, respectively). Therefore, the ileum sensitivity to contractile agents is differentially altered by the acute aerobic swimming exercise, without affecting the oxidative stress and the morphology of ileum smooth muscle.

Toxicological, Antidiarrheal and Spasmolytic Activities of Solanum paniculatum.

Solanum paniculatum is popularly known as "jurubeba-verdadeira". In folk medicine, its roots, stems, and leaves are used as tonics, anti-inflammatories, carminatives, diuretics, and for gastrointestinal disorders. This species is listed in the Brazilian Pharmacopoeia and belongs to the "Relação Nacional de Plantas Medicinais de Interesse ao SUS". Based on folk medicine data of the Solanum genus, we decided to investigate whether the crude ethanol extract from S. paniculatum aerial parts presents toxicological, antidiarrheal, and spasmolytic activities. The crude ethanol extract from S. paniculatum aerial parts did not produce in vitro or in vivo toxicity and showed dose-dependent antidiarrheal activity, inhibiting equipotently both the defecation frequency (ED50 = 340.3 ± 35.1 mg/kg) and liquid stool formation (ED50 = 370.1 ± 19.4 mg/kg) in mice. Conversely, the crude ethanol extract from S. paniculatum aerial parts did not inhibit normal intestinal transit, even though it has shown a dose-dependent reduction of both the castor oil-induced intestinal transit (Emax = 36.9 ± 1.3 %, ED50 = 242.0 ± 8.6 mg/kg) and intestinal fluid content (Emax = 74.8 ± 2.4 %, ED50 = 328.9 ± 15.9 mg/kg). Additionally, the crude ethanol extract from S. paniculatum aerial parts was approximately 2-fold more potent in antagonizing the phasic contractions induced with histamine (IC50 = 63.7 ± 3.5 µg/mL) than carbachol 10(-6) M (IC50 = 129.3 ± 14.1 µg/mL). Therefore, we concluded that the crude ethanol extract from S. paniculatum aerial parts presents antidiarrheal activity in mice related to the inhibition of small intestinal motility and secretion as well as nonselective spasmolytic activity on the guinea pig ileum.

Flavonoid galetin 3,6-dimethyl ether attenuates guinea pig ileum contraction through K(+) channel activation and decrease in cytosolic calcium concentration.

Flavonoid galetin 3,6-dimethyl ether (FGAL) has been isolated from the aerial parts of Piptadenia stipulaceae and has shown a spasmolytic effect in guinea pig ileum. Thus, we aimed to characterize its relaxant mechanism of action. FGAL exhibited a higher relaxant effect on ileum pre-contracted by histamine (EC50=1.9±0.4×10(-7) M) than by KCl (EC50=2.6±0.5×10(-6) M) or carbachol (EC50=1.8±0.4×10(-6) M). The flavonoid inhibited the cumulative contractions to histamine, as well as to CaCl2 in depolarizing medium nominally Ca(2+)-free. The flavonoid relaxed the ileum pre-contracted by S-(-)-Bay K8644 (EC50=9.5±1.9×10(-6) M) but less potently pre-contracted by KCl or histamine. CsCl attenuated the relaxant effect of FGAL (EC50=1.1±0.3×10(-6) M), but apamin or tetraethylammonium (1mM) had no effect (EC50=2.6±0.2×10(-7) and 1.6±0.3×10(-7) M, respectively), ruling out the involvement of small and big conductance Ca(2+)-activated K(+) channels (SKCa and BKCa, respectively). Either 4-aminopyridine or glibenclamide attenuated the relaxant effect of FGAL (EC50=1.8±0.2×10(-6) and 1.5±0.5×10(-6) M, respectively), indicating the involvement of voltage- and ATP-sensitive K(+) channels (KV and KATP, respectively). FGAL did not alter the viability of intestinal myocytes in the MTT assay and decreased (88%) Fluo-4 fluorescence, indicating a decrease in cytosolic Ca(2+) concentration. Therefore, the relaxant mechanism of FGAL involves pseudo-irreversible noncompetitive antagonism of histaminergic receptors, KV and KATP activation and blockade of CaV1, thus leading to a reduction in cytosolic Ca(2+) levels.

Essential oil from the leaves of Xylopia langsdorfiana (Annonaceae) as a possible spasmolytic agent.

Xylopia langsdorfiana A. St.-Hil. &Tul. (Annonaceae) is popularly known in the northeast of Brazil as 'pimenteira da terra', and an essential oil (XL-OE) was extracted from its leaves. Since Xylopia species are cited in folk medicine and diterpenes from X. langsdorfiana have spasmolytic activity, this study aimed to investigate a possible spasmolytic action of XL-OE on smooth muscle models. XL-OE (243 and 729 µg/mL) showed low pharmacologic efficacy on guinea pig trachea and rat aorta and uterus. However, in guinea pig ileum, XL-OE (27-729 µg/mL) inhibited carbachol or histamine-induced phasic contractions (1 µM) in a significant and concentration-dependent manner. In addition, XL-OE (81 µg/mL) reduced fluorescence intensity in ileal myocytes stimulated by histamine, indicating a decrease in cytosolic calcium concentration, which could explain the spasmolytic activity. Thus, XL-OE proved to be a promising natural product to be used in gastrointestinal diseases acting by modulating the cytosolic calcium concentration.

Relaxant effect of Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana A. St-Hil. & Tul., on tracheal smooth muscle.

Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana, has previously been shown to relax the guinea-pig trachea in a concentration-dependent manner. In this study we aimed to elucidate the mechanisms underlying this action and so contribute to the discovery of natural products with therapeutic potential. A possible interaction between diterpene and the Ca(2+)-calmodulin complex was eliminated as chlorpromazine (10(-6) M), a calmodulin inhibitor, did not significantly alter the diterpene-induced relaxation (pD2 = 4.38 ± 0.07 and 4.25 ± 0.07; mean ± S.E.M., n=5). Trachylobane-318 showed a higher relaxant potency when the trachea was contracted by 18 mM KCl than it did with 60 mM KCl (pD2 = 4.90 ± 0.25 and 3.88 ± 0.01, n=5), suggesting the possible activation of K(+) channels. This was confirmed, as in the presence of 10 mM TEA(+) (a non-selective K(+) channel blocker), diterpene relaxation potency was significantly reduced (pD2 = 4.38 ± 0.07 to 4.01 ± 0.06, n=5). Furthermore, K(+) channel subtypes KATP, KV, SKCa and BKCa seem to be modulated positively by trachylobane-318 (pD2 = 3.91 ± 0.003, 4.00 ± 0.06, 3.45 ± 0.14 and 3.80 ± 0.05, n=5) but not the Kir subtype channel (pD2 = 4.15 ± 0.10, n=5). Cyclic nucleotides were not involved as the relaxation due to aminophylline (pD2 = 4.27 ± 0.09, n=5) was not altered in the presence of 3 × 10(-5) M trachylobane-318 (pD2 = 4.46 ± 0.08, n=5). Thus, at a functional level, trachylobane-318 seems to relax the guinea-pig trachea by positive modulation of K(+) channels, particularly the KATP, KV, SKCa and BKCa subtypes.

Spasmolytic activity of trachylobanes ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid isolated from Xylopia langsdorfiana A. St-Hil. & Tul. (Annonaceae).

We aimed to investigate the possible spasmolytic activity of ent-7α-acetoxytrachyloban-18-oic acid (1) and ent-7α-hydroxytrachyloban-18-oic acid (2) on smooth muscle models. In male rat aorta and rat uterus, both diterpenes were unable to trigger spasmolytic action. However, 2 relaxed guinea-pig trachea: Compounds 1 and 2 antagonised, significantly and concentration-dependently, carbachol- and histamine-induced phasic contractions in guinea-pig ileum. Moreover, they induced a significant and concentration-dependent relaxation in pre-contracted (KCl, carbachol or histamine) guinea-pig ileum, with 2 being 15 times more potent than 1 in histamine-contracted ileum. These dissimilar results may be due to chemical differences between them. Thus, we demonstrated that 1 and 2 seem to be promising spasmolytic agents, although further studies are required to elucidate the spasmolytic action mechanism.

Ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid from Xylopia langsdorfiana A. St-Hil. & Tul. modulate K(+) and Ca(2+) channels to reduce cytosolic calcium concentration on guinea pig ileum.

In this study we investigated the mechanism underlying the spasmolytic action of ent-7α-acetoxytrachyloban-18-oic acid (trachylobane-360) and ent-7α-hydroxytrachyloban-18-oic acid (trachylobane-318), diterpenes obtained from Xylopia langsdorfiana, on guinea pig ileum. Both compounds inhibited histamine-induced cumulative contractions (slope=3.5±0.9 and 4.4±0.7) that suggests a noncompetitive antagonism to histaminergic receptors. CaCl(2)-induced contractions were nonparallelly and concentration-dependently reduced by both diterpenes, indicating blockade of calcium influx through voltage-dependent calcium channels (Ca(v)). The Ca(v) participation was confirmed since both trachylobanes equipotently relaxed ileum pre-contracted with S-(-)-Bay K8644 (EC(50)=3.5±0.7×10-(5) and 1.1±0.2×10-(5)M) and KCl (EC(50)=5.5±0.3×10-(5) and 1.4±0.2×10-(5)M). K(+) channels participation was confirmed since diterpene-induced relaxation curves were significantly shifted to right in the presence of 5mM tetraethylammonium (TEA(+)) (EC(50)=0.5±0.04×10-(4) and 2.0±0.5×10-(5)M). ATP-sensitive K(+) channel (K(ATP)), voltage activated K(+) channels (K(V)), small conductance calcium-activated K(+) channels (SK(Ca)) or big conductance calcium-activated K(+) channels (BK(Ca)) did not seem to participate of trachylobane-360 spasmolytic action. However trachylobane-318 modulated positively K(ATP), K(V) and SK(Ca) (EC(50)=1.1±0.3×10-(5), 0.7±0.2×10-(5) and 0.7±0.2×10-(5)M), but not BK(Ca). A fluorescence analysis technique confirmed the decrease of cytosolic calcium concentration ([Ca(2+)](c)) induced by both trachylobanes in ileal myocytes. In conclusion, trachylobane-360 and trachylobane-318 induced spasmolytic activity by K(+) channel positive modulation and Ca(2+) channel blockade, which results in [Ca(2+)](c) reduction at cellular level leading to smooth muscle relaxation.

Synthetic lapachol derivatives relax guinea-pig ileum by blockade of the voltage-gated calcium channels.

The present study was designed to further evaluate a possible spasmolytic activity of synthetic lapachol derivatives, norlapachol, alpha-norlapachone, beta-norlapachone and hydro-hydroxy-norlapachol (HH-norlapachol), on guinea-pig ileum. In guinea-pig ileum, except for norlapachol, all naphthoquinones inhibited the phasic contractions induced by carbachol or histamine. Even when the ileum was pre-contracted with KCl, carbachol or histamine, all naphthoquinones induced relaxation, suggesting that these naphthoquinones could be acting on the voltage-gated calcium channels (Ca(V)). As the tonic component this contraction is maintained mainly by the opening of the Ca(V), we hypothesized that these naphthoquinones might be acting on these channels. This hypothesis was confirmed by the observation that norlapachol (pD'2 = 4.99), alpha-norlapachone (pD'2 = 4.49), beta-norlapachone (pD'2 = 6.33), and HH-norlapachol (pD'2 = 4.53) antagonized the contractions induced by CaCl2 in depolarizing medium nominally without Ca2+. As beta-norlapachone was the most potent we decided to continue the study of its action mechanism. The fact that this naphthoquinone has inhibited the tonic contractions induced by S-(-)-Bay K8644 [EC50 = (1.6 +/- 0.30) x 10(-5) M] suggests that the Ca2+ channel involved belongs to the type L (Ca(V)1.2). In addition, in the functional level, the spasmolytic effect of beta-norlapachone does not involve participation of free radicals, since its curve of relaxation was unchanged in the presence of glutathione, an antioxidant agent.

Nb-benzoyltryptamine derivatives with relaxant activity in guinea-pig ileum.

A series of derivatives analogous to Nb-benzoyltryptamine were synthesized by the Schotten-Bauman procedure. The products obtained were: Nb-4-methoxy-benzoyltryptamine, Nb-2,4-dimethoxy-benzoyltryptamine, Nb-3,4-dimethoxy-benzoyltryptamine, Nb-3,4-methylenedioxy-benzoyltryptamine and Nb-3,4,5-trimethoxy-benzoyltryptamine. They were characterized through the usual spectrometric methods (UV, IR, 1H and 13C NMR) and showed non-selective relaxant activity in guinea-pig ileum pre-contracted with acetylcholine, histamine and KCl.