The source of ca2+ for the spasmolytic actions of longicaudatine,a bisindole alkaloid isolated from Strychnos trinervis (Vell.) Mart. (Loganiaceae)

Longicaudatine, a tertiary bisindole alkaloid isolated from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae), antagonized in a noncompetitive manner, carbachol and histamine induced contractions of the guinea-pig ileum and bradykinin responses in the rat uterus. The respective pD₂' values (mean ± SE) were 4.61 ± 0.21, 4.98 ± 0.04 and 4.49 ± 0.01. Longicaudatine, unlike verapamil, had no effect on voltage dependent Ca²⁺ channels, as it failed to inhibit KCI or CaCl₂ induced contractions of guinea-pig ileum and depolarized rat uterus respectively. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, longicaudatine produced a slower and weaker inhibition of noradrenaline induced sustained contractions of rabbit aortic strips. However, in the aorta, the alkaloid antagonized the intracellular calcium dependent transient contractions of noradrenaline and longicaudatine (IC₅₀, 5.01 × 10^?7 M) was approximately 133 times more potent that procaine (IC₅₀, 6.68 × 10^?5 M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Longicaudatine may exert nonspecific spasmolytic effects by acting on intracellular Ca²⁺ stores, rather than on depolarization dependent or receptor operated Ca²⁺ channels.     

Bisnordihydrotoxiferine and vellosimine from Strychnos divaricans root: Spasmolytic properties of bisnordihydrotoxiferine

Bisnordihydrotoxiferine and vellosimine, two tertiary indole alkaloids have been isolated from the root of Strychnos divaricans. Bisnordihydrotoxiferine antagonized in a nonspecific manner, oxytocin and acetylcholine induced contractions in the rat uterus and acetylcholine and histamine responses in the guinea-pig ileum. Bisnordihydrotoxiferine, like verapamil, produced effects on voltage dependent Ca²⁺ channels. For example in guinea-pig ileum, bisnordihydrotoxiferine (pD'₂ 3.92±0.09) and verapamil (pD'₂ 6.00±0.11) inhibited KCl induced contractions. Furthermore, bisnordihydrotoxiferine (pD'₂ 4.37±0.02) and verapamil (pD'₂ 6.83±0.10) also antagonized CaCl₂ induced contractions of K⁺-depolarized rat uterus. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, bisnordihydrotoxiferine had no effect. However, in the aorta, the alkaloid (IC₅₀, 6.10 × 10^?6M) antagonized the intracellular calcium dependent transient contractions of noradrenaline and it was about four times more potent than procaine (IC₅₀, 2.30 × 10^?5M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Bisnordihydrotoxiferine may produce nonspecific spasmolytic actions mainly by inhibiting intracellular calcium mobilization and to a lesser extent by inhibiting voltage dependent calcium channels in smooth muscles.     

Pharmacological Basis for Medicinal Use of Lens culinaris in Gastrointestinal and Respiratory Disorders

Crude extract of Lens culinaris (Lc.Cr), which tested positive for presence of anthraquinones, flavonoids, saponins, sterol, tannins, and terpenes exhibited protective effect against castor oil‐induced diarrhea in mice at 100–1000 mg/kg. In rabbit jejunum preparations, Lc.Cr caused relaxation of spontaneous contractions at 0.03–5.0 mg/mL. Lc.Cr inhibited carbachol (CCh, 1 μM) and K⁺ (80 mM)‐induced contractions in a pattern similar to dicyclomine, but different from verapamil and atropine. Lc.Cr shifted the Ca⁺⁺ concentration‐response curves to the right, like dicyclomine and verapamil. Pretreatment of tissues with Lc.Cr (0.03–0.1 mg/mL) caused leftward shift of isoprenaline‐induced inhibitory CRCs, similar to papaverine. In guinea‐pig ileum, Lc.Cr produced rightward parallel shift of CCh curves, followed by non‐parallel shift at higher concentration with suppression of maximum response, similar to dicyclomine, but different from verapamil and atropine. Lc.Cr (3.0–30 mg/kg) caused suppression of carbachol (CCh, 100 µg/kg)‐induced increase in inspiratory pressure of anesthetized rats. In guinea‐pig trachea, Lc.Cr relaxed CCh and high K⁺‐induced contractions, shifted CCh curves to right and potentiated isoprenaline response. These results suggest that L. culinaris possesses antidiarrheal, antispasmodic, and bronchodilator activities mediated possibly through a combination of Ca⁺⁺ antagonist, anticholinergic, and phosphodiesterase inhibitory effects, and this study provides sound mechanistic background to its medicinal use in disorders of gut and airways hyperactivity, like diarrhea and asthma. Copyright © 2014 John Wiley & Sons, Ltd.     

Further studies on the antidiarrhoeal activity of bisnordihydrotoxiferine,a tertiary indole alkaloid in rodents

The dimeric tertiary indole alkaloid bisnordihydrotoxiferine isolated from the root bark of Strychnos trinervis (Vell.) Mart. inhibited, on i.p. administration, Escherichia coli-induced diarrhoea and cholera toxin-stimulated intestinal fluid accumulation in mice. The respective ED₅₀ values were 10.6 and 20.0 mg/kg. The activity of bisnordihydrotoxiferine was unaffected by nalorphine or yohimbine, suggesting that the opioid and α₂-adrenoceptors respectively, are not important for its antidiarrhoeal action. In smooth muscle studies, bisnordihydrotoxiferine antagonized in a noncompetitive and reversible manner, the contractions produced by histamine, acetylcholine and substance P in guinea-pig ileum and by 5-hydroxytryptamine and arachidonic acid in rat fundic strip. The respective pD'₂ values (mean ± SEM) were 5.21 ± 0.29, 5.20 ± 0.29, 5.35 ± 0.12, in the ileum and 4.95 ± 0.13 and 3.66 ± 0.12 in the fundic strip. The values of slopes of the regression lines differed significantly from unity in all cases. Bisnor was inactive against PGE₂-induced contractions in the ileum. The mechanism of action of the alkaloid may be related to nonspecific antagonism of gastrointestinal smooth muscle stimulant activity of several endogenous substances.     

Effects of the essential oil of Croton zehntneri,and its constituent estragole on intestinal smooth muscle

The effects on isolated guinea-pig ileum of the essential oil of Croton zehntneri (CZEO) and of its main constituent estragole (57% of CZEO by weight) were studied. CZEO and estragole (0.1–100 μg/mL) decreased the tonus in 56% and 61.5%, respectively, of the muscles. At concentrations above 10 μg/mL, they induced spontaneous rhythmic movements of small amplitude (less than 11% of the potassium contraction peak to peak). At concentrations from 1 to 100 μg/mL and with similar potencies, these agents blocked the contractions induced by acetylcholine, histamine and 50 mM K⁺ and caused relaxation of already established potassium contractures. Tested separately, CZEO, estragole and anethole (28% of CZEO by weight) blocked the contraction induced by Ca⁺⁺ in the presence of 50 mM K⁺, but CZEO was more potent than estragole or anethole in blocking the Ca⁺⁺-induced contractions than those induced by K⁺. With large increases in the agonist concentration, the action of the oils on the contractions induced by Ca⁺⁺ was reversible; however, their effect on contractions induced by histamine or ACh was not. The data show that the essential oil of Croton zehntneri has an effect on intestinal smooth muscle that is predominantly antispasmodic, and attributable in part to the effect of estragole, a major constituent. © 1997 John Wiley & Sons, Ltd.     

Effect of ambrein on smooth muscle responses to various agonists

The pharmacological effects of ambrein (isolated from ambergris) on the contractile responses induced by some agonists in smooth muscle preparations were investigated. Ambrein in the concentration range of 10, 50 and 250 μg/ml decreased the spontaneous contraction of the isolated rabbit jejunum, rat uterus and guinea-pig vas deferens. Ambrein-induced antagonism to acetylcholine (Ach) in the guinea-pig ileum was abolished when the concentration of calcium chloride in the Tyrode's solution was increased to 5 mM/l. Furthermore, ambrein did not antagonise nicotine-induced contractions in the isolated rabbit jejunum or serotonin-induced contractions in the isolated guinea-pig ileum and vas deferens or the rat uterus. However, ambrein in the concentration range of 10, 50 and 250 μg/ml antagonised prostaglandins (PGs) E₂, D₂, F_2α, and oxytocin-induced contractions in the rat uterus in vitro. Ambrein also antagonised (±) noradrenaline and (−) adrenaline-induced contractions in the isolated guinea-pig vas deferens. It is concluded that ambrein-induced non-selective dose-dependent antagonism to the effects of some agonists (Ach, adrenaline, noradrenaline, PGs and oxytocin) in some smooth muscles may be due to the ability of this compound to interfere with the mobilisation of extracellular Ca²⁺ required for muscular contractions induced by these agonists.     

Selective modulatory effects of the essential oil of Croton zehntneri on isolated smooth muscle preparations of the guinea-pig

The effects of the essential oil of the plant Croton zehntneri (EOCz) in the concentration range 1–200 μg/mL were studied on the mechanical activity of various in vitro smooth muscle preparations of the guinea-pig. In isolated ileum EOCz induced a variable response such that in 57% of tissues basal tone was reduced (EC₅₀ 5 μg/mL) whereas the rest remained unaffected by the oil. In concentrations above 10 μg/mL EOCz induced spontaneous oscillatory contractions in all preparations. In contrast the basal tone of the aorta, portal vein and bladder remained unaltered by the oil. In the portal vein EOCz concentration-dependently inhibited the amplitude of spontaneous contractions (IC₅₀ 109 μg/mL) without reducing frequency, whereas in the bladder such activity was increased by the oil (EC₅₀ 44 μg/mL). In ileum precontracted with 60 mM KCl, EOCz induced a complete and concentration-dependent relaxation with an IC₅₀ value of approximately 26 μg/mL. In contrast EOCz did not relax KCl-induced tone in the aorta or bladder, whilst eliciting less than 20% relaxation of the precontracted portal vein. Thus our data show that EOCz exerts differential modulatory effects on the contractility of various smooth muscles of the guinea-pig. That EOCz appears to selectively relax intestinal smooth muscle may support its use in folk medicine as a gastrointestinal antispasmodic. © 1998 John Wiley & Sons, Ltd.     

有机硒化合物的抗炎及抗变态反应作用

 目的：有机硒化合物具有多种活性，为此研究3种合成的有机硒化合物的抗炎作用和抗变态反应作用,并分析构效关系。方法：药物对小鼠巴豆油性耳肿胀的影响;对组胺(histamine,His)、过敏性慢反应物质(slow-reacting substance of anaphylaxis SRS-A)所致离体豚鼠回肠收缩的影响;致敏豚鼠肺中SRS-A的提取及药物的拮抗实验。结果：3种化合物能不同程度地抑制小鼠巴豆油性耳肿胀(〖WTBX〗P＜0.05或P〖WTBZ〗＜0.01)。50%抑制离体豚鼠回肠收缩时的药物浓度(IC₅₀)分别为对His:1.25×10^-5,1.58×10^-4，1.25×10^-4 mol/L,对SRS-A:8.9×10^-6，1.25×10^-4，1.12×10^-4mol/L。致敏豚鼠肺释放SRS-A的抑制浓度:10^-4mol/L。结论：3药中9108对受体的拮抗作用最强。该类化合物的化学结构中苯环(B)邻位酯基取代的化合物具有强的受体拮抗作用。它们的抗炎及抗免疫作用与其对His及SRS-A的受体拮抗作用及SRS-A的阻释作用有关。     

Antispasmodic,bronchodilator and blood pressure lowering properties of Hypericum oblongifolium – possible mechanism of action

The crude extract of Hypericum oblongifolium (Ho.Cr), which tested positive for flavonoids, saponins and tannins caused concentration‐dependent (0.1–1.0 mg/mL) relaxation of spontaneous and high K⁺ (80 mM)‐induced contractions in isolated rabbit jejunum preparations, suggesting a Ca⁺⁺ antagonistic effect, which was confirmed when pretreatment of the tissue with Ho.Cr produced a rightward shift in the Ca⁺⁺ concentration‐response curves, like that caused by verapamil. Ho.Cr relaxed carbachol (1 μM) and high K⁺‐induced contractions in guinea pig tracheal preparations. It caused a dose‐dependent (3–100 mg/kg) fall in arterial blood pressure of rats under anesthesia. In isolated guinea pig atria, Ho.Cr caused inhibition of both atrial force and rate of spontaneous contractions. When tested in rabbit aortic rings, Ho.Cr exhibited a vasodilator effect against phenylephrine (1 μM) and high K⁺‐induced contractions. These results indicate that Ho.Cr possesses gastrointestinal, respiratory and cardiovascular inhibitory effects, mediated via a Ca⁺⁺ antagonist mechanism. Copyright © 2009 John Wiley & Sons, Ltd.     

Preliminary studies on the hydroalcoholic extract of the root of Cissampelos sympodialis Eichl in guinea-pig tracheal strips and bronchoalveolar leucocytes

The aqueous fraction of the ethanol extract of the root of Cissampelos sympodialis, reduced the spontaneous tone, and inhibited the contractions induced by submaximal concentrations of carbachol, histamine, prostaglandin F_2α and substance P, in guinea-pig tracheal preparations. The fraction was approximately equipotent to aminophyl-line and the IC₅₀ values of the above agents varied from 13.9 to 95.5 μg/mL, depending on the agonist used. In concentrations ranging from 1–100 μg/mL, the fraction also increased the intracellular levels of cyclic adenosine monophosphate in guinea-pig bronchoalveolar leucocytes. It is proposed that the combined effects on smooth muscles and on leucocytes indicate a pharmacological basis for the use of the plant in asthma.     

Effect of Extract of Leaf and Seed of Piper guineense on Some Smooth Muscle Activity in Rat,Guinea-pig and Rabbit

Extracts of the leaf and seed of Piper guineense were separately prepared and their pharmacological effects screened using smooth muscle of the gastrointestinal tract and uterus. The leaf extract enhanced both the frequency and tone of spontaneous contractions of rabbit jejunum and induced contraction of guinea-pig ileum, which were blocked by atropine. The seed extract had the opposite effect on rabbit jejunum, an inhibition which was antagonized by prazocin, and little or no effect on guinea-pig ileum. Both extracts had a stimulant effect on rat uterine muscle, the seed extract to a lesser extent.     

Pharmacological basis for the medicinal use of Zanthoxylum armatum in gut,airways and cardiovascular disorders

This study describes the gut, airways and cardiovascular modulatory activities of Zanthoxylum armatum DC. (Rutaceae) to rationalize some of its medicinal uses. The crude extract of Zanthoxylum armatum (Za.Cr) caused concentration‐dependent relaxation of spontaneous and high K⁺ (80 mM)‐induced contractions in isolated rabbit jejunum, being more effective against K⁺ and suggestive of Ca⁺⁺ antagonist effect, which was confirmed when pretreatment of the tissues with Za.Cr shifted Ca⁺⁺ concentration‐response curves to the right, like that caused by verapamil. Za.Cr inhibited the castor‐oil‐induced diarrhea in mice at 300–1000 mg/kg. In rabbit tracheal preparations, Za.Cr relaxed the carbachol (1 μM) and high K⁺‐induced contractions, in a pattern similar to that of verapamil. In isolated rabbit aortic rings, Za.Cr exhibited vasodilator effect against phenylephrine (1 μM) and K⁺‐induced contractions. When tested in guinea pig atria, Za.Cr caused inhibition of both atrial force and rate of spontaneous contractions, like that caused by verapamil. These results indicate that Zanthoxylum armatum exhibits spasmolytic effects, mediated possibly through Ca⁺⁺ antagonist mechanism, which provides pharmacological base for its medicinal use in the gastrointestinal, respiratory and cardiovascular disorders. Copyright © 2009 John Wiley & Sons, Ltd.     

Effects of Olea europaea L. extract on the rat isolated ileum and trachea

The effects of an Olea europaea L. dried leaf extract containing 3.2% of oleuropein were investigated on the rat isolated ileum and trachea. On basal tone rat isolated ileum, Olea europaea L. extract was shown to produce a dual effect characterized by a contraction at low doses (10^?7-10^?4g/mL) and a relaxation at high doses (3.10^?4-10^?3g/mL). The extract induced contractile effect was found to involve at least histamine, 5-hydroxytryptamine and thromboxane A₂. On precontracted rat isolated ileum, the extract only induced a relaxation that was not modified by nifedipine, diltiazem, dipyridamone, verapamil or papaverine (10^?6 M). The effects of the extract were also studied on the rat isolated trachea. On basal tone organs, Olea europaea L. extract did not produce any effect, whereas, when basal tone was raised by acetylcholine (ACh 10^?3 M), the drug caused a relaxation (maximal effect 39.01% ± 5.40%) of the response to theophylline; (3.10 ± 10^?3M n = 15). It is suggested that the induced relaxation is consecutive to an increase of intracellular 3′5′ cAMP.     

Studies on antidiarrheal and antispasmodic activities of Lepidium sativum crude extract in rats

This study was aimed to provide the pharmacological basis for the medicinal use of Lepidium sativum in diarrhea using in vivo and in vitro assays. The seed extract of Lepidium sativum (Ls.Cr) at 100 and 300 mg/kg inhibited castor oil‐induced diarrhea in rats. In isolated rat ileum, Ls.Cr (0.01–5 mg/mL) reversed carbachol (CCh, 1 µ m ) and K⁺ (80 m m )‐induced contractions with higher potency against CCh, similar to dicyclomine. Preincubation of rat ileum with a lower concentration of Ls.Cr (0.03 mg/mL) caused a rightward parallel shift in the concentration–response curves (CRCs) of CCh without suppression of the maximum response, while at the next higher concentration (0.1 mg/mL), it produced a non‐parallel rightward shift with suppression of the maximum response, similar to that of dicyclomine. Ls.Cr shifted the CRCs of Ca⁺⁺ to the right with suppression of the maximum response, similar to verapamil. These data suggest that Lepidium sativum seed extract possesses antidiarrheal and spasmolytic activities mediated possibly through dual blockade of muscarinic receptors and Ca⁺⁺ channels, though additional mechanism(s) cannot be ruled out and this study explains its medicinal use in diarrhea and abdominal cramps. Copyright © 2011 John Wiley & Sons, Ltd.     

Inhibitory effects of the sesquiterpene T-cadinol on contractile responses in the isolated guinea-pig ileum

The smooth muscle relaxing effect of the sesquiterpene T-cadinol, isolated from scented myrrh (resin of Commiphora guidottii Chiov., Burseraceae), was investigated. The compound inhibited the contractile responses in the isolated guinea-pig ileum to histamine, carbachol, Ba²⁺ and K⁺ in a concentration dependent and reversible manner. The antagonism of the receptor-mediated contractions induced by histamine and carbachol was not of a competitive type. The contractions induced by Ba²⁺- and K⁺ were somewhat more sensitive to the action of T-cadinol than the receptor mediated contractions. It is suggested that the compound may interfere with a step of the contraction sequence common to all four spasmogens.     

Evaluation of pharmacological activity of a crude hydroalcoholic extract from Jatropha elliptica

The pharmacological effect of the hydroalcoholic extract of Jatropha elliptica was analysed in in vivo and in vitro models. When given orally in mice, the extract showed a low acute toxicity (LD₅₀ 5 g/kg). In a dose of 0.5 or 1 g/kg p.o. the extract did not interfere with diuresis in the rat, but was found to be effective in blocking rat paw oedema induced by carrageenan and partially, serotonin-induced oedema. In the same dose, the extract failed to inhibit rat paw oedema induced by dextran and the increase of rat cutaneous vascular permeability caused by Bothrops Jararaca venom, dextran, histamine, PAF-acether and serotonin. Pre-incubation of the isolated rat uterus and guinea-pig ileum with the extract (0.2–0.8 mg/mL), produced a concentration-related and non-competitive inhibition of contractions induced by acetylcholine and bradykinin. However, the extract was about 2-fold more potent in inhibiting the contraction of both agonists in guinea-pig ileum than in rat uterine muscle. In rat aorta, the extract (50–100 μg/mL) caused a concentration-dependent inhibition of noradrenaline-evoked contractions, being about 5-fold more potent when compared to the IC₅₀ values obtained in rat uterus.     

Pharmacological Studies on the Antispasmodic,Bronchodilator and Anti‐Platelet Activities of Abies webbiana

This study evaluated the antispasmodic, bronchodilator and anti‐platelet activities of Abies webbiana to rationalize some of its folk uses in gut and airways disorders and inflammation. The crude extract of A. webbiana (Aw.Cr) caused a complete relaxation of both spontaneous and K⁺ (80 mM)‐induced contractions in isolated rabbit jejunum in a concentration‐dependent manner. Aw.Cr shifted the Ca⁺⁺ concentration–response curves (CRCs) to the right, in a fashion similar to verapamil, confirming its Ca⁺⁺ channel blocking (CCB) effect. In isolated rabbit tracheal preparations, it caused relaxation of carbachol (1 μM) and K⁺ (80 mM)‐induced contractions comparable to verapamil suggesting that the bronchodilatory effect may possibly be mediated through CCB activity. Aw.Cr was found to be the inhibitor of both ADP‐ and epinephrine‐induced aggregation of human platelets thereby suggesting therapeutic potential in this plant against thrombo‐embolic conditions. The exhibited anti‐platelet effect was observed at low doses against epinephrine as compared to ADP. This study confirmed the presence of spasmolytic activity in Abies webbiana through possible blockade of Ca⁺⁺ channels providing evidence for its folkloric use in gut and respiratory disorders in addition to anti‐platelet activity. Copyright © 2014 John Wiley & Sons, Ltd.     

Spasmolytic Activity of Cissampelous mucronata Leaf Extract

The aqueous leaf extract of Cissampelous mucronata (Menispermaceae) was studied for spasmolytic properties. The extract inhibited the responses of histamine, acetylcholine and nicotine on the guinea-pig ileum in a dose-related manner. The extract completely abolished the spontaneous pendular movement of the rabbit jejunum reversibly, and decreased gastrointestinal motility in mice. It did not modify the effect of Ca²⁺ on the guinea-pig ileum. Acute toxicity tests in mice established the i.p. LD₅₀ value of the extract to be 1698.24±77 mg/kg.     

Smooth muscle relaxant activities of compounds isolated from malaysian medicinal plants on rat aorta and guinea-pig ileum

Muscle relaxant activities of six compounds isolated from Malaysian medicinal plants were investigated on the smooth muscles of the rat aorta and longitudinal muscle of the guinea-pig ileum. Except for goniothalamin, the other five compounds exhibited varying degrees of muscle relaxant activities on the two smooth muscles. Dicentrine, isocorydine, altholactone and usnic acid reduced the contractions to KCI and phenylephrine in the rat aorta, whilst atranorin slightly reduced the contractions to phenylephrine but not KCI. In addition, dicentrine and isocorydine markedly reduced the contractile response to phenylephrine in Ca²⁺-free Krebs solution. In the longitudinal muscle of the guinea-pig ileum, altholactone, atranorin, dicentrine and isocorydine inhibited to a greater extent the phasic than the tonic responses to KCI. All four compounds similarly inhibited the contractions induced by ACh. The results suggest that the relaxant activities of the compounds are attributed mainly to inhibition of Ca²⁺ influx via the calcium channels in the membrane of the smooth muscles. Furthermore, the greater sensitivity of dicentrine, isocorydine and altholactone against phenylephrine-induced contractions or KCI-induced phasic contractions are due to their abilities to inhibit intracellular Ca²⁺ release in these muscles.     

Differential antagonistic effect of hydroalcoholic extract from Hymenaea martiana hayne arzeik on kinin and other agonist-induced contractions of the isolated rat uterus and Guinea-pig ileum

This study was undertaken to evaluate the action of the hydroalcoholic extract (HE) from the bark of Hymenaea martiana on bradykinin (BK), lysyl-bradykinin (L-BK), acetylcholine (ACh), angiotensin II (AII), prostaglandin F_2a (PGF_2a), serotonin (5-HT), oxytocin (Ot) and histamine (His)-induced contractions of the isolated rat uterine muscle and guinea-pig ileum. The HE (50–200 μg/mL) added to the bath for 20 min caused a concentration-dependent rightward displacement of BK, L-BK and ACh-induced contractions in the rat uterus, allied to a discrete but significant reduction of maximal responses to the latter two agonists. By contrast, at the same range of concentrations the HE antagonized in a concentration-dependent but noncompetitive manner the contractions induced by AII, but only at high concentrations (200 μg/mL) it significantly inhibited contractions evoked by both PGF_2a and Ot, while contractile responses induced by 5-HT were not affected. In the guinea-pig ileum, the HE of H. martiana (50 and 100 μg/ml) caused a discrete rightward displacement of the BK and ACh concentration—response curves. Higher concentrations of the HE of H. martiana (200 μg/mL) caused a marked depression of BK and ACh-induced maximal responses. These findings show that the active principle(s) presents in the HE from the bark of H. martiana exhibits an interesting pharmacological profile against several neurotransmitter-induced contractions in nonvascular smooth muscles. Such actions may be relevant for supporting, at least in part, the use of this plant in folk medicine.