Mechanism of action of the aqueous seed extract of Mucuna pruriens on the guinea-pig ileum

The hot water extract (HWE) of the seed of Mucuna pruriens dose-dependently contracted the guinea-pig ileum. The ED₅₀ and pD₂ values for the HWE was lower than those of ACh and histamine. Cyproheptadine and promethazine (10 ng/mL) significantly antagonized the effects of histamine, 5-hydroxytryptamine (5-HT) and HWE. Atropine blocked the effect of ACh and partially blocked the HWE. The calcium channel blockers nifedipine and verapamil both blocked the effects of all the agonists including HWE. These results suggest that the HWE contains potent histamine receptor stimulants or principles as it was blocked by low doses of H₁ receptor blockers. It appears that stimulation of the receptors leads to influx of calcium since the effect was also blocked by nifedipine and verapamil. It is likely that it also stimulates muscarinic receptors. © 1997 John Wiley & Sons, Ltd.     

Oxytocic and oestrogenic effects of Monechma ciliatum methanol extract in vivo and in vitro in rodents

Various solvent extracts of the leaves of Monechma ciliatum (family Acanthecaea) were tested for oxytocic properties on uterine preparations in vivo and in vitro. The methanol extract (HME) contracted the nonpregnant uterus of the rat, guinea-pig and mouse as well as preparations obtained from guinea-pigs on days 6–7 and 11–12 of pregnancy. The rat pregnant uterus was not affected by the extract. Oral administration of HME to rats on days 15, 16 and 17 of pregnancy had no abortifacient effect compared with oxytocin. However, laparotomy on day 23 revealed fetal death in utero. The extract was also found to have oestrogenic activity based on parameters such as uterine weight ratio, premature vaginal opening and degree of vaginal cornification.     

Uterine relaxant effects of Curcuma aeruginosa Roxb. rhizome extracts

The effects and plausible mechanism of action of Curcuma aeruginosa Roxb. (Zingiberaceae) rhizome chloroform and methanol extracts on the uterine contraction were investigated using isolated uterus strips from estrogen primed rats. The contractile responses were recorded isometrically with a Grass FT03 force transducer connected to a MacLab system. The experiments were carried out on both nonstimulated, agonist- and KCl-stimulated uteri. In the nonstimulated uterus, the two extracts (10–400 μg/ml) had no significant effect. In contrast, in the stimulated uterus, the chloroform and methanol extracts exerted concentration-dependent inhibition of the contractions induced by oxytocin (1 mU/ml), prostaglandin F_2α (PGF_2α, 0.5 μg/ml), ACh (3 × 10⁻⁶ M) and KCl (40 mM) with the IC₅₀ (inhibition of force) of 31.4, 58.59, 56.21 and 29.28 μg/ml; and 57.79, 69.3, 223.8 and 69.19 μg/ml, respectively. Verapamil, the reference L-type calcium channel blocker, exhibited a similar pattern of inhibition with the IC₅₀ of 0.03, 0.25, 0.35 and 0.04 μg/ml. The IC₅₀ of diclofenac against a PGF_2α-induced contraction was 31.36 μg/ml. It is known that the contraction induced by agonists and KCl is mainly due to calcium influx through the voltage-gated L-type calcium channels opened indirectly or directly by agonist–receptor activation and KCl. Thus, it is speculated that the two plant extracts might inhibit uterine contraction by interrupting the influx of Ca²⁺ probably through voltage-gated L-type calcium channels. This possibility was further substantiated by the ability of the extracts to shift the CaCl₂–contraction curves to the right. As the methanol extract also reduced the contraction of oxytocin in Ca²⁺-free EDTA solution; thus, it is suggested that part of its action may be involved with an intracellular mechanism. The effect of the two extracts did not involve the activation of β₂-adrenoceptors since their effects were unaffected by propranolol. Based on the inhibitory effect of the extracts on the oxytocin-induced contraction, it is concluded that the extracts might be useful as tocolytic agents for the prevention of preterm labor. Their effects on the inhibition of PGF_2α-induced contractions also seem useful for the treatment of dysmenorrhea. There are reports by others that the plant rhizome contains β-pinene and sesquiterpenes. In addition, there is evidence that these compounds possess spasmolytic effects in the rat intestine and uterus. Therefore, the uterine relaxant effect of the plant extracts could be due to β-pinene and some sesquiterpene lactones contents. The methanol extract is less potent than the chloroform extract, and this might be due to the lower amount of terpene compounds or different compounds may involve in this action.     

In vitro determination of the uterine stimulatory effect of the aqueous leaf extract of Ficus exasperata

Ethnopharmacological relevance

The leaves of Ficus exasperata Vahl (Moraceae) are used by traditional healers in Southern Nigeria to arrest pre-term contractions and are also used as an abortifacient in some parts of Africa.

Aim of study

An earlier study on the aqueous leaf extract of Ficus exasperata (AET) showed that the extract at lower concentrations inhibited oxytocin-induced uterine contractions and at higher concentrations, stimulated uterine contraction. This study thus aims to determine, the possible mechanisms by which AET stimulates uterine contraction in vitro.

Materials and methods

The contractile effect of AET (5.0 × 10⁻² to 100 × 10⁻² mg/ml) and oxytocin (which was used as a reference drug) were examined in the presence of the following antagonists: atropine (1.18 and 11.91 nM); indomethacin (1.42 and 14.25 nM); verapamil (2.03 and 20.35 nM); phentolamine (4.09 and 40.91 nM), or diphenhydramine (4.45 and 44.47 nM). The EC₅₀ and E_max were determined and statistically analyzed using one-way ANOVA and Dunnett post hoc test.

Results

There was no significant difference in the EC₅₀ and E_max of AET and oxytocin in the presence of atropine. Diphenhydramine and phentolamine significantly inhibited (p < 0.01) the extract but both drugs had no effect on oxytocin. However, significant differences (p < 0.01) were observed in the EC₅₀ and E_max of AET and oxytocin in the presence of verapamil and indomethacin.

Conclusions

These results suggest that the stimulation of uterine contractility by AET may arise from the activation of histamine H₁- and/or α-adrenergic receptors, interference with calcium channels and/or stimulation of prostaglandin synthesis in utero.     

Activity of aqueous extract of the bark of Vitex doniana on uterine muscle response to drugs

The activity of Vitex doniana on the uterine muscle response was investigated. The bark of Vitex doniana was extracted in boiled water at 100 degrees C, and the extracted solution filtered and centrifuged with refrigeration. The extract prepared from the dry powder extract was tested on uterine muscle strip preparations. The bark extract of Vitex doniana was analysed elementally and found to contain much more potassium and phosphate than calcium, magnesium, zinc and iron. The presence of potassium ions in excess may also be partly responsible for the effect of the crude extract on uterine muscle activity. In another study, Vitex doniana extract induced graded uterine muscle contractions and also potentiated the contractile effects of prostaglandins, ergometrine and oxytocin. However, the potentiating effect was not significant on the contractile responses to acetylcholine and potassium chloride. The investigation therefore suggests that the effect of the Vitex doniana bark extract may be not only voltage operated but may act via uterotonic receptors. Therefore, the use of Vitex doniana to control postpartum bleeding after child birth may be justified.     

Effect of kauranes from Montanoa spp. on rat uterus

The effect of kaurenoic acid (from Montanoa frutescens), grandifloric and kauradienoic acid (from M. tomentosa) and 16α-hydroxy-ent-kauran-19-oic acid and its methyl ester (from M. hibiscifolia) were assayed on the contractions of rat uterus induced by acetylcholine, oxytocin and serotonin. The four kauranes assayed inhibited the contractile activity induced by the three agonists through a mechanism independent of either β₂-adrenergic or H₂-histaminergic receptors present in uterine smooth muscle. Oestrogenized uteri treated with kauradienoic acid underwent histological changes including epithelial flattening and desquamation.© 1997 John Wiley & Sons, Ltd.     

The Anticonceptive and the Effect on Uterus of Ether Extract, 18312-J of Ricinus communis

The ether extract 18312-J of Ricinus communis seed (600 mg/kg and 1.2 g/kg) administered subcutaneously to rats possessed significant anticonceptive activity. The extract demonstrated an oestrogenic effect in immature ovariectomized rats and mice and was devoid of any antioestrogenic property. Furthermore, the extract did not induce a decidual response in oestrogen primed ovariectomized rats and did not inhibit deciduoma formation in rats treated with progesterone. Administration of 18312-J to rats significantly altered the activity profile of the uterine muscle with respect to the frequency and amplitude of contraction as well as decreased responsiveness to oxytocin, ergometrine, acetylcholine and transmural electrical stimulation (TNS, 1-20H_z). The anticonceptive effect of 18312-J may be due in part to a disturbance of the oestrogen/progesterone balance and as well as to a direct action on the uterus. © 1997 by John Wiley & Sons, Ltd.     

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.     

选择性5-羟色氨受体抑制剂——巴西苏木红素(英文)

目的:子宫平滑肌内存在多种5-HT受体,5-HT通过作用于5-HT受体实现其对子宫收缩活性的影响。本研究探讨巴西苏木红素对5-HT受体的作用及其特点。方法:小鼠分离子宫平滑肌条,采用受体拮抗实验和real time PCR方法,对巴西苏木红素的5-HT受体的抑制作用进行研究。结果:巴西苏木红素虽然对正常子宫平滑肌的收缩幅度和频率无影响,但能明显抑制5-HT2受体激动剂马来酸麦角新碱的收缩活性,其pA2为5.71±0.21。而5-HT亚型的选择性激动剂舒马普坦(5-HT1D)、AL34662(5-HT2A)、MCPP(5-HT2C)的收缩子宫活性同样能够被巴西苏木红素抑制,pA2分别为4.58±0.06;4.91±0.15;5.38±0.15。巴西苏木红素明显抑制了5-HT受体1D和2C亚型mRNA的表达。结论:巴西苏木红素能够阻滞小鼠子宫5-HT受体,并通过可能影响5-HT受体所介导的子宫功能。     

吴茱萸汤醇提各组分止呕活性的研究

目的 :对吴茱萸汤醇提各组分止呕活性的研究和机制初步探讨。方法 :采用硫酸铜诱导家鸽呕吐实验 ,小鼠胃排空实验 ,ACh和 5-HT作用的离体大鼠胃条实验来确定其中具有止呕活性的组分 ,并观察有效组分对ACh ,5-HT ,组胺累积浓度 效应曲线的影响。结果 :50%醇洗脱液和 70%醇洗脱液有十分显著性的止呕效应 ,且副作用较小 ,对ACh ,5-HT ,组胺累积浓度 效应曲线均有一定的作用。结论 :50%醇洗脱液和 70%醇洗脱液含有的止呕活性成分较多 ,50%和 70%醇可以从吴茱萸汤中提取较多止呕活性成分 ,止呕作用可能与拮抗ACh ,5-HT ,组胺受体有关。     

CNS depressant effects,anti-inflammatory activity and anti-cholinergic actions of Santolina chamaecyparissus extracts

The pharmacological activity of several extracts together with the lyophilized infusion of S. chamaecyparissus ssp. squarrosa were investigated. The lethal dose 50% (LD₅₀), effect on animal metabolism, mechanical and thermic analgesia and spontaneous, anti-inflammatory, and anti-ulcer activity have been determined. Studies on isolated organs (rat duodenum and rat uterus) were also carried out. The hexanic and chloroformic extracts were potent antagonists of the thermic analgesia test; the former extract was also active in the mechanical analgesia test. The chloroformic extract and, to a lesser extent, the ethyl acetate extract and lyophilized infusion demonstrated noteworthy activity as anti-inflammatory agents. No extract produced an ulcerogenic effect. The hexanic extract had the highest inhibitory effect on ACh induced contraction of rat duodenum and the ethyl acetate extract of oxytocin induced contraction of rat uterus.     

Effects of moxibustion at different times on prostaglandin and vasopressin levels in uterine tissues of rats with dysmenorrhea due to cold-dampness retention

Objective

To observe the effects of moxibustion at different times on prostaglandin E₂ (PGE₂), prostaglandin F_2α (PGF_2α) and arginine vasopressin (AVP), in the uterine tissues of rats with dysmenorrhea due to cold-dampness retention, and to explore the differences and possible mechanisms of moxibustion at different times in easing pain in dysmenorrhea due to cold-dampness retention.

Methods

Forty-three female Wistar rats were randomly divided into a blank control group (n=7), a model group (n=9), a pre-moxibustion group (n=9), an immediate-moxibustion group (n=9) and a pre-moxibustion plus immediatemoxibustion group (n=9). Rat models of primary dysmenorrhea due to cold-dampness retention were established using (0±1) °C ice water immersion method combined with injection of estradiol benzoate for 10 d, followed by injection of oxytocin on the 11th day. Rats in the 3 intervention groups received moxibustion to Shenque (CV 8) and Guanyuan (CV 4), 10 min for each acupoint, once a day. Rats in pre-moxibustion group were given mild moxibustion, beginning on the 8th day during modeling, for 3 continuous days; rats in immediate-moxibustion group were given one time mild moxibustion, immediately after injection of oxytocin on the 11th day during modeling; rats in pre-moxibustion plus immediate-moxibustion group were given mild moxibustion, beginning on the 8th day during modeling till immediately after injection of oxytocin on the 11th day during modeling, for 4 continuous days. The level of PGF_2α in the rat uterine tissues was measured by enzyme-linked immunosorbent assay (ELISA), and the levels of PGE₂ and AVP in rat uterine tissues were measured by radioimmunoassay.

Results

Compared with the blank control group, the levels of PGF_2α and AVP, the PGF_2α/PGE₂ ratio in the model group were significantly increased (P<0.01), and the PGE₂ level was significantly decreased (P<0.01) in the rat uterine tissues in the model group. Compared with the model group, the writhing latency was significantly prolonged, the writhing number and the total writhing score were all decreased in the pre-moxibustion group, the immediate-moxibustion group and the pre-moxibustion plus immediate-moxibustion group (all P<0.01); the levels of PGF_2α and AVP, and the PGF_2α/PGE₂ ratio were all significantly decreased (P<0.05, P<0.01), and the PGE₂ level was significantly increased (P<0.01) in the rat uterine tissues of the 3 treatment groups. Compared with the pre-moxibustion group, the writhing number and the total writhing score were all decreased in the immediate-moxibustion group and the pre-moxibustion plus immediate-moxibustion group (all P<0.01), the writhing latency was significantly prolonged in the pre-moxibustion plus immediate-moxibustion group(P<0.01); the levels of PGF_2α and PGF_2α/PGE₂ ratio were significantly decreased (P<0.05, P<0.01), and the PGE₂ level was significantly increased (P<0.01) in rat uterine tissues in the immediate-moxibustion group and the pre-moxibustion plus immediate-moxibustion group. Compared with the immediate-moxibustion group, the writhing latency was significantly prolonged and the writhing number was decreased (all P<0.05), and the total writhing score was decreased (P<0.01) in the pre-moxibustion plus immediatemoxibustion group; the PGF_2α level and the PGF_2α/PGE₂ ratio were significantly decreased (P<0.01), and the PGE₂ level was significantly increased (P<0.01) in rat uterine tissues in the pre-moxibustion plus immediate-moxibustion group.

Conclusion

Moxibustion at different times all can produce obvious analgesic effects on dysmenorrhea due to cold-dampness retention in rats, and pre-moxibustion plus immediate-moxibustion ranks the top. The mechanism of this analgesic effect may be via the regulation of abnormal PGF_2α, PGE₂ and AVP levels, to effectively inhibit the spastic contraction of uterine smooth muscle in dysmenorrhea rat, thereby improving the ischemia and hypoxia in uterus.

     

Effect of papaya latex extract on gravid and non-gravid rat uterine preparations in vitro

In search of uterotonic principles, papaya (Carica papaya, Caricaceae) latex extract (PLE) was tested on rat uterine preparations in vitro at various stages of the estrous cycle and gestation periods. Rat uterine contractile activity was remarkably increased by different doses of PLE in proestrus and estrus stages compared to metestrus and diestrus stages of the estrous cycles. The maximum contractile activity of the uterus was observed at the later stages of pregnancy which correspond with the peak level of estrogen in the plasma. A direct dose-dependent spasmodic action with increased frequency and amplitude was observed with PLE in all non-gravid uterine preparations. Pretreatment of the tissue with phenoxybenzamine (PB) non-competitively blocked the effect of PLE. Blocking of the 5-HT receptors with methysergide partially blocked the excitatory response to PLE. Pretreating the tissue with Indomethacin, a cyclo-oxygenase inhibitor, had no effect on the response to PLE. The release of PLE induced mast cell degranulation and subsequent release of heparin, biogenic amines or prostaglandins (PGs) was ruled out by pretreating the tissue with sodium cromoglycate, a mast cell stabilizer. Pure papain induced uterine contractions were not sustained for a longer period and at higher concentrations the receptor proteins were affected by the enzymatic action of papain. From this study it is evident that the crude papaya latex contain a uterotonic principle which might be a combination of enzymes, alkaloids and other substances which can evoke sustained contraction of the uterus acting mainly on the alpha adrenergic receptor population of the uterus at different stages.     

Effect of instant moxibustion on the levels of prostaglandin and arginine vasopressin in the uterine tissues of dismenorrhea rats with cold-damp congealing and stagnation type

Objective

To observe the effect of instant moxibustion on the levels of prostaglandin E₂ (PGE₂), prostaglandin F2α (PGE_2α) and arginine vasopressin (AVP) in the uterine tissues of dismenorrhea rats with cold-damp congealing and stagnation type and to explore its possible mechanism.

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.     

Effects on rat uterine and aorta strip smooth muscle of Thymus leptophyllus extract

The diethylether extract from Thymus leptophyllus was found to be more active on uterine smooth muscle than on aorta strips. Rat uterus experiments with and without extracellular calcium, yielded similar IC₅₀ values. A non-specific mechanism for the relaxant activity can therefore be postulated. In rat aorta and in the presence of extracellular calcium the extract inhibited the contractile response induced by K⁺ depolarizing solution and had a less inhibitory effect on noradrenaline (NA) contraction. In a Ca²⁺-free solution the extract strongly reduced the Ca²⁺-release induced by NA, but it did not affect the transient contraction caused by caffeine (CAF).     

Uterotonic effects of hydromethanolic extract of Parquetina nigrescens (Periplocaceae) on spontaneous contractile activity in the isolated myometrium of pregnant rats

Parquetina nigrescens (Afz.) Bullock (Periplocaceae) hydromethanolic extract (PAR) in reference solution exerts a stimulating and spasmogenic action on the pregnant rat myometrium in vitro. This action is characterised by increasing amplitude of spontaneous isometric contractions and a slight elevation of muscular basic tonus. These effects on myometrium may be compared with those provoked by sulprostone (PGE₂) in the same experimental conditions. In calcium free solution, Parquetina nigrescens extract could restore partially spontaneous contractile activity. On the contrary, in presence of EDTA PAR induces a complete abolition of the activity. On the other hand, in calcium free solution, sulprostone is able to develop a clear elevation of basic tonus (contracture). These observations support the hypothesis that the extract has an oxytocin-like effect, which is characterised by an extracellular influx of calcium, responsible for the increase of the maximum isometric contraction amplitude. Sulprostone activates both extracellular and intracellular calcium responsible for the increase of contractile activity and development of the contracture of uterine smooth muscle.     

艾叶不同提取物对小鼠原发性痛经的影响

目的:通过观察艾叶不同提取物(水提液、95％醇提液、先水提后95％醇提混合液)对痛经模型小鼠的影响,初步探讨艾叶治疗原发性痛经的作用机制.方法:ICR雌性小鼠随机分为9组,分别是正常组、模型组、阳性药西乐葆45.0 mg·kg -1组、艾叶不同提取物的高、低剂量组(1.65,0.55 g·kg-1).除正常组外,其余各组以10 mg·kg-1的剂量给小鼠sc苯甲酸雌二醇连续7d,第8天给予ip缩宫素10 mL·kg-1制造原发性痛经模型.各组均在造模第5天起,每天ig给予不同药物连续4d,观察艾叶不同提取物对原发性痛经模型小鼠的扭体次数以及对子宫组织匀浆中一氧化氮(NO)和钙离子(Ca2+)水平的影 响.结果:与模型组相比,艾叶醇提物高剂量、先水提后醇提混合液的高、低剂最对原发性痛经小鼠的痛阈有极显著的提高,扭体反应抑制率分别为36.9％,52.5％,42.2％(P＜0.01),且相同剂量下先水提后醇提混合液的作用优于水提液(P＜0.05);此外艾叶醇提物高剂量、先水提后醇提混合液的高、低剂量组能显著增加子宫组织内NO含量,降低Ca2+含量(P＜0.01).结论:艾叶提取物制法不同,对原发性痛经模型小鼠的镇痛作用强度不同.在3种不同提取物中,先水提后醇提混合液药效最强,醇提液次之,水提液最弱,这可能与其溶出的效应物质不同有关.     

连翘对豚鼠离体回肠运动的影响

目的:观察连翘对豚鼠离体肠管运动的影响,以期探讨其止呕作用的机制。方法:以呕吐相关受体激动剂为工具药,利用离体恒温浴槽,观察连翘对豚鼠离体回肠收缩的影响。结果:连翘能够抑制离体肠管的自发活动,表现为收缩张力降低,并呈剂量依赖性关系。乙酰胆碱(acetylcholine,Ach)、组织胺(histamine,His)、五羟色胺(5-hydroxytryptamine,5-HT)能够兴奋肠管,使张力升高、振幅变大,连翘高(10 g·L-1)、中(5 g·L-1)、低(2 g·L-1)剂量均能抑制以上3种工具药所致肠管收缩,降低其收缩张力和振幅,但对频率无明显影响。多巴胺(dopamine,DA)能够抑制肠管收缩,表现为张力降低、振幅变小,连翘高剂量和中剂量能够拮抗DA的肠管松弛作用,使张力升高、振幅变大;连翘低剂量能够进一步使张力降低,但使振幅增大。结论:连翘可以抑制豚鼠回肠运动,其机制可能是通过阻断肠平滑肌上的M受体、H1受体、5-HT受体和D2受体,也可能是对肠管的直接抑制作用,其止呕机制尚待进一步深入研究。