Histamine H3 receptors regulate acetylcholine release from the guinea pig ileum myenteric plexus.

The effect of selective histamine H3-receptor agonists and antagonists on the acetylcholine release from peripheral nerves was evaluated in the guinea pig longitudinal muscle-myenteric plexus preparations, preloaded with (3H)choline. In the presence of H1 and H2 blockade, histamine (10(-7)-10(-4) M) and (R)-alpha-methylhistamine (10(-8)-10(-6) M) inhibited the electrically-evoked acetylcholine release, being (R)-alpha-methylhistamine more active than histamine, but behaving as a partial agonist. The effect of histamine was completely reversed by selective H3-blocking drugs, thioperamide and impromidine, while only submaximal doses of (R)-alpha-methylhistamine were antagonized. Furthermore, thioperamide and impromidine enhanced the electrically-evoked acetylcholine release. On the contrary, the new H3-blocker, HST-7, was found substantially ineffective, both as histamine antagonist and as acetylcholine overflow enhancer. These data suggest that histamine exerts an inhibitory control on the acetylcholine release from intestinal cholinergic nerves through the activation of H3 receptors.     

Different mechanisms are responsible for the contractile effects of histaminergic compounds on isolated intestinal smooth muscle cells

The effects of histamine and dimaprit on intestinal smooth muscle contractility were investigated on isolated cells from longitudinal muscle of the guinea pig ileum. Both histamine (10⁻¹⁴–10⁻¹⁰ M) and dimaprit (10⁻¹³–10⁻¹⁰ M) exerted a concentration-dependent contraction of intestinal cells, causing a maximum decrease in cell length of about 20%. This effect was not significantly different from that induced by cholecystokinin-octapeptide (CCK-8) 10⁻⁹ M. The concentration-response curves to histamine and dimaprit were shifted to the left in the presence of the histamine H₂-receptor antagonist famotidine (10⁻⁷ M) indicating the occurrence in the smooth muscle of H₂ receptors mediating relaxation. Whereas the contraction produced by histamine was competitively antagonized by the H₁ receptor antagonist mepyramine (10⁻⁸ M), neither mepyramine (10⁻⁷ M) nor temelastine (10⁻⁷ M) did modify the contractile effect of dimaprit. In contrast, atropine (10⁻⁸ M) significantly depressed the maximum response to dimaprit without affecting that exerted by histamine. These data indicate that histamine and dimaprit can modify intestinal contractility, by acting via different mechanisms; while the contractile action of histamine is related to H₁ receptor activation, that produced by dimaprit involves cholinergic pathways.     

Contractile and relaxant effects of dimaprit on guinea pig isolated intestinal cells

The effect of the histamine H₂ receptor agonist dimaprit on intestinal contractility was characterized on smooth muscle cells isolated from the longitudinal muscle of the guinea pig ileum. Dimaprit exerted two opposite effects on the contractility of isolated muscle cells: relaxation of cholecystokinin octapeptide (CCK-S)-induced contractions in the range of concentrations 10⁻¹⁷-10⁻¹³ M and contraction at concentrations higher than 10⁻¹³ M. The relaxant effect of dimaprit was totally prevented by the H₂ blocker famotidine (10⁻⁷ M), which, at the same time, enhanced the contractile effect of dimaprit, shifting to the left the concentration-response curve to the agonist. This contraction was not modified by the histamine H₁ receptor antagonists pyrilamine and temelastine, tested both at 10⁻⁷ M. By contrast, atropine 10⁻⁸ M abolished the contractile effect of dimaprit, while leaving unchanged the response to CCK-8. Our results clearly indicate that longitudinal muscle cells of the guinea pig ileum possess inhibitory H₂ receptors, which can be activated by very low concentrations of dimaprit; moreover, they revealed that dimaprit can have non-histaminergic effects, probably due to muscarinic receptor activation; however, concentrations about 10000 times higher than those necessary to activate H₂ receptors, are required.     

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.     

Vasoactive intestinal polypeptide: increased tone, enhancement of acetylcholine release, and stimulation of adenylate cyclase in intestinal smooth muscle

Vasoactive intestinal polypeptide (VIP) was examined $\text{in vitro}$ for effects on tone and neuronal release mechanisms in intestinal smooth muscle since this is a site of high peptide concentration. VIP contracted the guinea pig ileum and rabbit jejunum in concentrations ranging from 10^?9 to 10^?7 M. Increased tone in the guinea pig ileum was partially antagonized by the anticholinergic agent, atropine (4.38 × 10^?6 M) suggesting that one component of the contractile response was due to the indirect release of acetylcholine. The H₁ receptor antagonist, pyrilamine, did not alter the increased tone produced by VIP indicating that histamine release did not contribute to the ileal contractile response and that VIP exerted a selective effect to enhance neuronal release of acetylcholine. The ability of VIP to modulate acetylcholine release was confirmed in field stimulated ileal preparations where VIP increased the force developed to endogenously released acetylcholine without altering the direct response to acetylcholine. In rabbit jejunum and ileal smooth muscle, VIP related cyclic AMP levels. However, inhibition of phosphodiesterase with papaverine did not potentiate either the VIP-induced ileal contraction or enhancement of the field stimulated response. This raises the possibility that increases in intestinal cyclic AMP may be involved more in VIP-induced alterations in ion transport or secretory phenomenon than in intestinal motility. These studies describing the ability of VIP to modulate acetylcholine release and to increase ileal tone are consistent with the proposed role of VIP in intestinal patholgies involving excessive mucous secretion and motility.     

Inhibitory effects of hot water extract of the Stevia stem on the contractile response of the smooth muscle of the guinea pig ileum

The effects of a hot water extract of the stem of Stevia rebaudiana on the smooth muscle of isolated guinea pig ileum were investigated. The butyl alcohol layer of the extract antagonized the contractions of the isolated guinea pig ileum induced by histamine (1 x 10(-5) M) and acetylcholine (1 x 10(-5) M) in a concentration-dependent manner. The butyl alcohol layer of the extract also showed inhibition of CaCl(2) (1 x 10(-3)-3.8 x 10(-1) M)-induced contractions. The antagonism of the extract was considered to be non-specific, but this action might be related to an influx of extracellular Ca(2+).With column chromatography preparation, the active component was assumed to be as stevioside. The antagonistic effects exerted by the stem extract of Stevia rebaudiana contributed to the gastroprotective activity of the extract in animals fed dietary histamine.     

Lithium does not synergize the peripheral action of cholinomimetics as seen in the central nervous system

Lithium is known to synergize the action of cholinomimetics in the CNS such that pilocarpine induces seizures in low concentration (1/13th of per se dose) in rats. The present study was undertaken to see if lithium priming also enhances the peripheral effects of acetylcholine and pilocarpine i.e. change in blood pressure in rats and contractions of the isolated guinea pig ileum. In anaesthetized rats the blood pressure was recorded from cannulated carotid artery connected through the pressure transducer to Coulbourn polygraph. The blood pressure response of pilocarpine was not different either in magnitude or in duration when administered 1, 2 and 4 h after lithium chloride (3 meq/kg) pretreatment as compared to the control. Similarly acetylcholine effect remained unchanged after lithium chloride priming. In the isolated guinea pig ileum experiments, ileum was incubated for 1 h in different concentrations of lithium chloride and effect on acetylcholine induced contractions were observed. Lithium in concentration of 2.8 x 10(-3) M had no effect on acetylcholine induced contractions while incubation with higher concentrations of 1.4 x 10(-2) M and 2.8 x 10(-2) M significant inhibition of acetylcholine contractions were observed. At this concentration, histamine induced contractions were also inhibited. The results indicate that lithium does not synergize the action of cholinomimetics in the periphery as that seen in the CNS. The inhibition of acetylcholine and histamine induced contractions in guinea pig ileum at high concentration of lithium seems to be non-specific effect.     

Pharmacology of L-660,711 (MK-571): a novel potent and selective leukotriene D4 receptor antagonist

L-660,711 (3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl) ((3-dimethyl amino-3-oxo propyl)thio)methyl)thio)propanoic acid is a potent and selective competitive inhibitor of [3H]leukotriene D4 binding in guinea pig (Ki value, 0.22 nM) and human (Ki value, 2.1 nM) lung membranes but is essentially inactive versus [3H]leukotriene C4 binding (IC50 value in guinea pig lung, 23 microM). Functionally it competitively antagonized contractions of guinea pig trachea and ileum induced by leukotriene (LT) D4 (respective pA2 values, 9.4 and 10.5) and LTE4 (respective pA2 values, 9.1 and 10.4) and contractions of human trachea induced by LTD4 (pA2 value, 8.5). L-660,711 (5.8 x 10(-8)M) antagonized contractions of guinea pig trachea induced by LTC4 in the absence (dose ratio = 28) but not in the presence of 45 mM L-serine borate (dose ratio less than 2). L-660,711 (1.9 x 10(-5)M) did not block contractions of guinea pig trachea induced by histamine, acetylcholine, 5-hydroxytryptamine, PGF2 alpha, U-44069, or PGD2. In the presence of atropine, mepyramine, and indomethacin, L-660,711 (1.9 x 10(-5)M) inhibited a small component of the response to antigen on guinea pig trachea but completely blocked anti-IgE-induced contractions of human trachea. L-660,711 (i.v.) antagonized bronchoconstriction induced in anesthetized guinea pigs by i.v. LTC4, LTD4, and LTE4 but did not block bronchoconstriction to arachidonic acid, U-44069, 5-hydroxytryptamine, histamine, or acetylcholine. Intraduodenal L-660,711 antagonized LTD4 (0.2-12.8 micrograms/kg)-induced bronchoconstriction in guinea pigs, and p.o. L-660,711 blocked LTD4- and Ascaris-induced bronchoconstriction in conscious squirrel monkeys and ovalbumin-induced bronchoconstriction in conscious sensitized rats treated with methysergide (3 micrograms/kg). The pharmacological profile of L-660,711 indicates that it is a potent, selective, orally active leukotriene receptor antagonist which is well suited to determine the role played by LTD4 and LTE4 in asthma and other pathophysiologic conditions.     

Histaminergic effect of crude papaya latex on isolated guinea pig ileal strips.

In the present study, we investigated the effect of the crude latex of Carica papaya L. (CPX) on isolated guinea pig ileal strips. CPX (0.5-512 microg/ml) caused concentration-dependent contraction of ileal strips suspended in Tyrode solution. The concentration of atropine (0.69 microM) that significantly blocked the contractile effect of acetylcholine on the isolated guinea pig ileum showed no significant effect on CPX- and histamine-induced contractions of the ileal strips. Mepyramine (87.6 nM) significantly blocked the contractile effect of histamine and CPX on the ileum. The same concentration of mepyramine, however, had no significant effect on acetylcholine-induced contraction of the isolated ileal strips. Removal of Ca2+ from the bathing medium abolished ileal contractions induced by acetylcholine, histamine and CPX. All the test substances were able to provoke ileal contractions after replacement of the Ca(2+)-free solution with Tyrode solution. Furthermore, 10(-5) M of nifedipine, a Ca(2+)-entry antagonist, reversibly inhibited the contractile effect of all the test substances on the ileal strips. Results of this study together appear to show that CPX-induced contraction of the isolated guinea pig ileum is mediated via H1-receptors and dependent on extracellular Ca2+ influx.     

Studies on the loss of sensitivity in smooth muscle.

Specificity of desensitization effect was investigated at guinea pig ileum using the desensitizing agonists acetylcholine, carbachol, histamine, and serotonine. The desensitization with acetylcholine markedly diminished the contraction effects to test doses of all tested agonists. Contrary to acetylcholine, the histamine desensitization is mainly specific, the serotonine desensitization is a complete specific effect. A different influence of the tested agonists on intracellular ions is discussed.     

Selective stimulation of histamine H3 autoreceptors

A simple derivative of histamine, alpha-methylhistamine i.e. 4-(2-aminopropyl)-imidazole, was shown to potently inhibit the K+-induced release of [3H] histamine from slices of rat cerebral cortex previously incubated in the presence of [3H] histidine. The maximal inhibition elicited by alpha-methylhistamine was of about 60% i.e. similar to that elicited by exogenous histamine. The effect occurred with an EC50 value of 4.3 +/- 1.1 X 10(-9) M about 10 times lower than that of histamine and was reversed by a H3-receptor antagonist. Since alpha-methylhistamine is known to display negligible potency at H1- and H2-receptors, this compound appears to be the first highly potent and selective H3-receptor agonist to be identified.     

Effect of L-prolyl-L-leucyl-glycinamide (MIF-I) on some neutrotransmitter-receptor interactions

Some neurotransmitter-receptor interactions have been studied in an attempt to determine how L-prolyl-L-leucyl-glycinamide (MIF-I) exerts its antiparkinson effect. MIF-I affected neither the contractile responses of isolated mouse vas deferens and guinea pig ileum to noradrenaline, acetylcholine, substance P and histamine, nor the inhibitory effects of dopamine and GABA on the rat vas deferens and guinea pig ileum. MIF-I, as well as L-leucine and Pro-Leu, antagonized the contractile response of the ileum to 5-hydroxytryptamine (5-HT). Behavioural tests were used to examine the action of MIF-I on CNS transmitter-receptor interactions. MIF-I did not modify the circling produced by either dopamine agonists in nigro-striatal lesioned rats of 5-HT agonists in rats with a lesion of the medial raphe nucleus. MIF-I affected neither 5-hydroxytryptophan-induced head twitches in mice, which is a measure of 5-HT receptor stimulation, nor striatally-evoked head turning in the rat, which is a model for brain GABA function. It is concluded that MIF-I, at the doses used, does not directly modify the function of any of the CNS transmitter examined. Other possibilities to explain its antiparkinson action are discussed.     

Effect of cholecystokinin octapeptide and somatostatin on the motility of guinea pig and canine gallbladder

Species differences have been observed in the effect of cholecystokinin octapeptide (CCK OP) on the canine and guinea pig gallbladder smooth muscle motility. 1. CCK OP was more potent stimulant in canine than in guinea pig gallbladder smooth muscles. Its pD2 values were 10 and 9.2, respectively. 2. The acetylcholine (10(-4) M)-induced maximum contractions in canine gallbladder muscle strips were by 50% lower as compared to the CCK OP (10(-8) M) maximum responses while in guinea pig gallbladder muscle strips the acetylcholine (ACh) maximum responses were by 20% lower than the CCK OP maximum responses. 3. CCK OP increased [3H]ACh release by 27% in canine gallbladder and by 40% in guinea pig gallbladder. 4. Somatostatin (SOM) had not any direct myogenic effect in guinea pig and canine gallbladder but it decreased [3H]ACh release from gallbladder intrinsic cholinergic neurons.     

Isolation and characterization of smooth muscle cell membranes

A method for the isolation of guinea pig ileum smooth muscle cell membranes is described. The plasma membrane fraction possessed a (Na⁺, K⁺)-ATPase which was inhibitied by ouabain. The Mg²⁺-dependent ATPase of the membrane fraction was stimulated by 1 μM Ca²⁺. A basal ATPase, not dependent on Mg²⁺, was directly stimulated by Ca²⁺ in the range of 1 μM to 1 mM.The isolated membranes contracted in response to the following substances: ATP, angiotensin II and some of its analogs, bradykinin, acetylcholine and histamine. The contractility was inhibited by ouabain and chlorambucil-angiotensin II, but not by cytochalasin B. No contraction was produced by AMP, angiotensin I and adrenaline.     

Clonidine-induced coronary vasodilatation in isolated guinea pig heart is not mediated by endothelial alpha2 adrenoceptors.

Functional role of endothelial alpha(2)-adrenoceptor in coronary circulation remains unclear. Clonidine, an agonist of alpha(2)-adrenoceptors, was reported to induce coronary vasodilatation via stimulation of endothelial alpha(2)-adrenoceptors or coronary vasoconstriction involving vascular smooth muscle alpha(2)-adrenoceptors. Moreover, H(2) receptor-dependent responses to clonidine were described. Here, we reassess the contribution of endothelial alpha(2)-adrenoceptor and H(2) receptors to coronary flow and contractility responses induced by clonidine in the isolated guinea pig heart. We found that clonidine (10(-9) - 10(-6) M) produced concentration-dependent coronary vasoconstriction without a significant change in contractility. This response was inhibited by the alpha(1)/alpha(2)-adrenoceptor antagonist - phentolamine (10(-5) M) and the selective alpha(2)-adrenoceptor antagonist yohimbine (10(-6) M), but it was not changed by the selective alpha(1)-adrenoceptor antagonist prazosin (10(-6) M). In the presence of nitric oxide synthase inhibitor, L-NAME (10(-4) M) the clonidine-induced vasoconstriction was potentiated. Clonidine at high concentrations of 10(-5) - 3 x 10(-5) M produced coronary vasodilatation, and an increase in myocardial contractility. These responses were abolished by a selective H(2)-receptor antagonist, ranitidine (10(-5) M), but not by phentolamine (10(-5) M). We conclude that in the isolated guinea pig heart, clonidine-induced vasoconstriction is mediated by activation of smooth muscle alpha(2)-adrenoceptors whereas clonidine-induced coronary vasodilatation is mediated by activation of vascular H(2) histaminergic receptors. Accordingly, endothelial alpha(2)-adrenoceptors does not seem to play a major role in coronary flow response induced by clonidine.     

Isolation, partial purification and pharmacodynamics of a slow contractile substance in the venom sac extract of the wasp Vespa cincta Fabr

The venom of V. cincta contains acetylcholine (ACh), histamine and 5-hydroxytryptamine (5-HT). Blockers of these agonists did not block completely the hypotensive and smooth muscle contractile activity of venom. On smooth muscle, there was a residual slow contraction. The active substance which produced this slow contraction was separated by solvent extraction, gel filtration and TLC. The purified material (which has been provisionally designated "Vecikinin") lowered cat, rat and guinea pig blood pressure, increased amplitude of cardiac contraction, and increased capillary permeability. Vecikinin contracted several smooth muscle preparations (rat uterus, rat ascending colon, guinea pig ileum, guinea pig colon and rat ileum), while relaxing rat duodenum. Its contractile activity was not lost on boiling, but acid or alkali-boiling reduced its contractile activity. It was inactivated on incubation with chymotrypsin and carboxypeptidase but not with trypsin, pepsin or leucine aminopeptidase. It is a peptide, appears to be of low molecular weight, and could be distinguished from substance P, angiotensin, bradykinin and hornet or wasp kinin.     

Biochemical and pharmacological activities of SSR 146977, a new potent nonpeptide tachykinin NK3 receptor antagonist

SSR 146977 is a potent and selective antagonist of the tachykinin NK3 receptor. In Chinese hamster ovary cells expressing the human tachykinin NK3 receptor, SSR 146977 inhibited the binding of radioactive neurokinin B to NK3 receptors (Ki = 0.26 nM), senktide (10 nM) induced inositol monophosphate formation (IC50 = 7.8-13 nM), and intracellular calcium mobilization (IC50 = 10 nM). It antagonized [MePhe7]neurokinin B induced contractions of guinea pig ileum (pA2 = 9.07). Senktide (30 nM) induced firing rate increase of noradrenergic neurons in the guinea pig locus coeruleus and dopaminergic neurons in the guinea pig substantia nigra was also blocked by SSR 146977 (50 and 100 nM, respectively). In vivo, in the respiratory system, SSR 146977 inhibited bronchial hyperresponsiveness to acetylcholine, bronchial microvascular permeability hypersensitivity to histamine (doses of 0.1-1 mg/kg i.p.), and cough (doses of 0.03-1 mg/kg i.p.) provoked by citric acid in guinea pigs. In the central nervous system, SSR 146977 inhibited turning behaviour (ID50 = 0.2 mg/kg i.p. and 0.4 mg/kg p.o.) and prevented the decrease of locomotor activity (10 and 30 mg/kg i.p) mediated by the stimulation of NK3 receptors in gerbils. In guinea pigs, SSR 146977 antagonized senktide-induced acetylcholine release in the hippocampus (0.3 and 1 mg/kg i.p) and norepinephrine release in the prefrontal cortex (0.3 mg/kg i.p.). It also prevented haloperidol-induced increase of the number of spontaneously active dopamine A10 neurons (1 and 3 mg/kg i.p.).     

Identification and specific blockade of histaminergic receptors in guinea pig vasa deferentia

Histamine produces contractions of the guinea pig vas deferens. The present investigation was undertaken to characterize the nature of histaminergic receptors in this tissue. Histamine (1.6 X 10(-6) M to 3.2 X 10(-5) M) produced dose-related contractions of guinea pig vas deferens (GPVD). Mepyramine (5.3 X 10(-8) M and 1 X 10(-9) M) blocked the responses to histamine competitively. Metiamide (1.23 X 10(-5) M) did not block the responses to histamine significantly. Specific H1 and H2 receptor agonists, namely 2-(2'-pyridyl)ethylamine (PEA) (2.55 X 10(-6) M to 3.0 X 10(-5) M) and 4-methylhistamine (4-MH) (2.52 X 10(-5) M to 3.0 X 10(-4) M), respectively, produced dose-related contractions of GPVD. The responses to PEA were blocked competitively by mepyramine, whereas the responses to 4-MH were blocked by metiamide. Reserpine pretreatment (5 mg/kg, i.p., 24 h) did not alter the responses to histamine and PEA. Our data suggest the presence of both H1 and H2 receptors in the GPVD which are excitatory in nature.     

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.     

Spasmolytic and tonic effect of Iberogast® (STW 5) in intestinal smooth muscle

STW 5 (Iberogast^®) is a fixed combination of nine medicinal plant extracts effective in the treatment of functional dyspepsia and irritable bowel syndrome. The effects of STW 5, a combination of Iberis amara fresh plant extract, and other eight plant extracts as well as single extract components including extracts from Menthae piperitae folium, Matricariae flos and Liquiritiae radix, were assayed in guinea pig ileum with or without stimulation with acetylcholine or histamine, in order to find a possible effect on the contractility of intestinal smooth muscle.STW 5 decreased acetylcholine- and histamine-induced contraction of guinea pig ileum. This was also true for extracts of Menthae piperitae folium, Matricariae flos and L. radix. Extract from I. amara, however, showed no spasmolytic action; in contrary, it increased the basal resting tone and contraction of atonic ileal segments. This was also true when STW 5 was employed.A spasmolytic action of STW 5 could also be observed in duodenum, jejunum and colon.These data are the first to show not only the spasmolytic effects of STW 5 and its component extracts in intestinal muscle but also the tonicising effects of STW 5 through its component Iberis amara extract in relaxed intestinal muscle. Thus, pharmacological evidence suggests a dual-action principle and may explain, at least in part, the clinically observed therapeutic efficacy of STW 5 (Iberogast^®) in both hypotonic and spastic dysmotility symptoms of functional dyspepsia and irritable bowel syndrome.