Ultrasonographic assessment of metoclopramide effect on gastric volume in parturients females undergoing Caesarean section: a randomized double blind study.

BACKGROUND: The prokinetic effect of metoclopramide promotes gastric emptying and decreases stomach capacity. The aim of the present study was to assess the efficacy of metoclopramide in reducing gastric contents and volume using gastric point-of-care ultrasonography (PoCUS) in parturients females prepared for elective Cesarean section under general anesthesia. METHODS: A total of 111 parturient females were randomly allocated to one of two groups. The intervention group (Group M; N.=56) received 10 mg metoclopramide diluted in 10 mL 0.9% normal saline. The control group (Group C; N.=55): received 10 mL 0.9% normal saline. The cross-sectional area and volume of stomach contents were measured using ultrasound before and one hour after the administration of metoclopramide or saline. RESULTS: Statistically significant differences in mean antral cross-sectional area and gastric volume were observed between the two groups (P<0.001). Group M had significantly lower rates of nausea and vomiting compared to the control group. CONCLUSIONS: Metoclopramide decreases gastric volume, reduces postoperative nausea and vomiting, and may lower the risk of aspiration when used as premedication before obstetric surgery. Preoperative gastric PoCUS has utility in objectively assessing stomach volume and contents.

Use of AgNOR staining to determine the effect of metoclopramide on neural tube development in early chick embryos.

Nausea and vomiting during pregnancy are common problems and prolonged pharmacological treatment often is needed; however, the teratogenic effects of anti-emetic drugs on neural tube (NT) development are not clear. We investigated the effects of different doses of metoclopramide on NT development in 48 and 72 h chick embryos using an argyrophilic nucleolar organizing region (AgNOR) staining method. We used 150 fertile, specific pathogen-free eggs incubated for 28 h, then randomly divided into five equal groups: group A, sham control was administered 0.9% saline; groups B - E were administered 0.15 mg/egg, 0.3 mg/egg, 0.6 mg/egg and 1.2 mg/egg, respectively. Half of the eggs in each group were taken from the incubator at 48 h incubation and the other half at 72 h incubation. After incubation, eggs were opened, embryos were dissected from their membranes, fixed with 10% formalin and examined by light microscopy. The NT status, i.e., open or closed, and somite number, crown-rump length, morphological features and gross developmental abnormalities were recorded. Excised embryos were sectioned and stained using hematoxylin and eosin or the AgNOR procedure and examined for morphology and histopathology. Delayed NT closure was observed in all 48 h drug exposed embryos, but in the 72 h groups, this occurred only in high-dose groups. Somite number was reduced significantly in groups C - E compared to the control group. Crown-rump length was decreased in both 48 and 72 h embryos. We found a decreased total AgNOR area:nuclear area ratio in 48 and 72 h embryos of all experimental groups. We found that metoclopramide delayed NT closure in chick embryos in a dose-dependent manner.

Use of prokinetic agents in hospitalised adult patients: A scoping review.

BACKGROUND: Gastrointestinal motility is important for adequate uptake of fluids and nutrition but is often impaired in hospitalised patients. Prokinetic agents enhance gastrointestinal motility and are prescribed for many hospitalised patients. In this scoping review, we aimed to systematically describe the body of evidence on the use of prokinetic agents in hospitalised patients. We hypothesised, that the body of evidence would be limited and derive from heterogeneous populations. METHODS: We conducted this scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews statement. We searched Medline, Embase, Epistemonikos and the Cochrane Library for studies assessing the use of prokinetic agents on any indication and outcome in adult hospitalised patients. We used a modified version of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. RESULTS: We included 102 studies with a total of 8830 patients. Eighty-six studies were clinical trials (84%), and 52 (60%) of these were conducted in the intensive care unit, with feeding intolerance as the main indication. In the non-intensive care setting the indications were wider; most studies assessed use of prokinetic agents before gastroscopy to improve visualisation. The most studied prokinetic agent was metoclopramide (49% of studies) followed by erythromycin (31%). In total 147 outcomes were assessed with only 67% of the included studies assessing patient-centred outcomes, and with gastric emptying as the most frequently reported outcome. Overall, the data provided no firm evidence on the balance between the desirable and undesirable effects of prokinetic agents. CONCLUSIONS: In this scoping review, we found that the studies addressing prokinetic agents in hospitalised adults had considerable variations in indications, drugs and outcomes assessed, and that the certainty of evidence was judged to be low to very low.

Metoclopramide as a Potential Antipsychotic Against Long-Term Methionine Exposure in Zebrafish.

Methionine (MET) contributes to brain function and is required for proper functioning of the central nervous system. However, exceptionally high levels of MET and its metabolites in plasma have been found to be toxic and can lead to cell alterations. Long-term exposure to MET has been shown to mimic psychotic symptoms in schizophrenic patients and rodents. The present study evaluated behavioral and neurochemical effects of long-term exposure to MET in zebrafish. Five groups of zebrafish were exposed to MET at a concentration of 4.5 mM for 7 days, along with acute exposure to 25 µM of clozapine and 750, 1000, and 1250 µM of metoclopramide. In contrast, the normal group was exposed to only water and dimethyl sulfoxide. After the treatment, social interaction, anxiety, memory, and locomotion of zebrafish and serotonin levels in zebrafish brains were evaluated. Our results showed that metoclopramide was not only beneficial in improving MET-induced cognitive impairment but it also prevented social withdrawal in zebrafish exposed to MET. In addition, metoclopramide reversed anxiety-like behavior, as indicated by significant changes in locomotion activity. Despite slight changes in serotonin levels in the zebrafish brain, an in vitro serotonin assay failed to demonstrate significant differences between the disease control, normal, and two treatment groups. Finally, results from the study showed that repeated administration of MET induced schizophrenia-like symptoms, although metoclopramide ameliorated the MET-mediated negative symptoms and cognitive deficits in zebrafish. Overall, our findings suggest a new perspective to further explore the antipsychotic properties of metoclopramide.

Safe Use of Erythromycin For Refractory Gastroparesis After Small Bowel Transplantation.

Current therapeutic options with prokinetic agents for posttransplant gastroparesis are limited. Erythromycin is associated with adverse reactions, including corrected QT interval prolongation and cytochrome P450 3A4 isoenzyme inhibition. The use of erythromycin has been avoided in patients undergoing treatment with cyclosporine or tacrolimus because of significant fluctuations in therapeutic immunosuppression levels. We report herein the successful use of erythromycin after visceral transplant to treat delayed gastric emptying. Two patients were managed with oral erythromycin (initial dose of 750 mg/d divided into 3 doses) for gastroparesis after visceral transplant. Patient 1 was a woman aged 42 years with a history of chronic intestinal pseudo-obstruction syndrome who underwent isolated small bowel transplant with dual (gastric and duodenal) proximal allograft anastomosis. Posttransplant gastroparesis was initially managed with oral metoclopramide. The patient also required high doses of tacrolimus (36 mg/d) to maintain adequate immunosuppression levels. The decision was made to change metoclopramide to erythromycin, which significantly decreased the daily tacrolimus dose requirement (from 36 to 9 mg/d), with resolution of nausea and intermittent bloating symptoms. Patient 2 was a woman aged 35 years with ultra-short gut syndrome after extensive enterectomy due to intestinal volvulus who underwent uneventful combined intestinal and colon transplant. Conventional pharmacologic therapy for gastroparesis was initiated after surgery without success. Erythromycin was started 15 days posttransplant, with significant improvement in her symptoms, and discontinued 47 days post-transplant. To maintain therapeutic levels (8-10 mg/dL), daily tacrolimus dose was decreased 75.8% and 36.5% for patients 1 and 2, respectively. No significant side effects associated with erythromycin use were observed in either patient. Our findings here suggest that erythromycin may be safely used for gastroparesis after small bowel transplant. Close monitoring of immunosuppressive drug levels and dose adjustments of other medications affected by inhibition of cytochrome P450 3A4 are advised.

Effects of GnRHa and hCG with or without dopamine receptor antagonists on the spawning efficiency of African catfish (Clarias gariepinus) reared in hatchery conditions.

Optimization of artificial reproduction is essential for minimizing genetic diversity, especially when fish are captured from their natural habitats and spawned in controlled conditions. In the present study, there was evaluation of the effects of gonadotropin-releasing hormone analogue (GnRHa) and human chorionic gonadotropin (hCG) with or without dopamine receptor antagonists such as domperidone (DOM) and metoclopramide (MET) on the spawning efficiency of African catfish (Clarias gariepinus) reared in captivity. The control group was intramuscularly (IM) injected with 1 mL of sterile saline solution. The fish specimens of the other six groups were injected IM with GnRHa or hCG, or in combination with either DOM or MET. None of the specimens had ovulations in the control group. There was the longest latency period in specimens treated with only GnRHa or hCG. There were the largest egg mass weight, fecundity, and hatchability (%) in specimens of the GnRHa + MET group. These findings indicate that GnRHa or hCG combined with dopamine receptor antagonists such as DOM and MET resulted in a marked enhancement of ovulation rate and increased the egg mass, fecundity, and hatchability of the treated C. gariepinus, and the values when there was inclusion of the MET treatment exceeded those when there was treatment with DOM.

The anti-cancer effect of metoclopramide on triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancers. Chemotherapy is the most important therapeutic option for TNBC, and chemotherapy-induced nausea and vomiting (CINV) is inevitable. Metoclopramide is a good and cost-effective therapeutic option for chemotherapy-induced nausea and vomiting. However, it is not commonly used in breast cancer because it can increase serum prolactin levels by blocking dopamine D2 receptor. This study aimed at elucidating the effect of metoclopramide on triple-negative breast cancer, MDA-MB-231 cells were treated with various concentrations of metoclopramide, the cell proliferation was detected by MTT method, the apoptosis rate was detected by Annexin V/PI double staining method, the expression change of death-related protein was detected by Western Blot. We found that metoclopramide inhibits cell proliferation and induces cell apoptosis of MDA-MB-231 in a concentration-dependent manner, and the Bcl family was involved in this process.

Is the use of recombinant cGnRH may be a future alternative to control the fish spawning? Let us go with the goldfish example.

The use of recombinant gonadotropin-releasing hormone (rGnRH) has very rarely been tested in fish to promote spawning. This study evaluated the impact of recombinant chicken gonadotropin-releasing hormone (rcGnRH) with metoclopramide on the release of sex steroids and final maturation induction in goldfish (Carassius auratus) broodstock. For this purpose, goldfish broodstock was divided into four groups and treated with 0.9% NaCl with 20 mg/kg metoclopramide (Met) (C); 10 µg/kg body weight (BW) rcGnRH with 20 mg/kg metoclopramide (rcGn10); 15 µg/kg BW rcGnRH with 20 mg/kg metoclopramide (rcGn15); and 20 µg/kg BW rcGnRH with 20 mg/kg metoclopramide (rcGn20). The capability of the rcGnRH for eliciting biological response was tested in vivo by evaluating the changes of 17ß estradiol (E2), testosterone (T), and 17α, 20ß-dihydroxy-4-pregnen-3-one (DHP) and the induced spawning. Blood samples were obtained at 0 h, 12 h, and 24 h after injection. The rcGn10, rcGn15, and rcGn20 treatments induced lower E2 concentration, especially 24 h post-injection. T levels were significantly higher in rcGn10, rcGn15, and rcGn20 treatments 12 h post-injection than at 0 h and then decreased at 24 h post-injection. Furthermore, the rcGnRH tested significantly enhanced DHP secretion in rcGn10, rcGn15, and rcGn20 treatments 12 h post-injection before a decline at 24 h post-injection. No significant difference between the sampling times was found in the C treatment for the 3 sex steroids tested. The results also displayed that rcGnRH at 10-20 µg/kg of body weight can trigger spawning with the highest speed and efficiency of spawning at 20 µg/kg. The obtained results represent a possible strategy for enhancing the artificial reproduction and ovulation of broodstock fish by rGnRH and further support the use of recombinant hormones to promote reproduction in aquaculture.

Cardiovascular effects of metoclopramide and domperidone on human 5-HT4-serotonin-receptors in transgenic mice and in human atrial preparations.

It is unclear whether metoclopramide and domperidone act on human cardiac serotonin 5-HT4-receptors. Therefore, we studied transgenic mice that only express the human 5-HT4 receptor in cardiomyocytes in the atrium and in the ventricle (5-HT4-TG), their wild type-littermates (WT) and isolated human atrial preparations. We found that only metoclopramide but not domperidone enhanced the force of contraction in left atrial preparations (pEC50 = 6.0 ± 0.1; n = 7) from 5-HT4-TG, isolated spontaneously beating right atrial preparations (pEC50 = 6.1 ± 0.1; n = 7) from 5-HT4-TG, Langendorff perfused hearts from 5-HT4-TG, living 5-HT4-TG and human right atrial muscle preparations obtained during bypass surgery of patients suffering from coronary heart disease. The maximum inotropic effect of metoclopramide was smaller (81 ± 2%) than that of 5-HT on the left atria from 5-HT4-TG. The maximum increase in the beating rate due to metoclopramide was 93 ± 2% of effect of 5-HT on right atrial preparations from 5-HT4-TG. Metoclopramide and domperidone were inactive in WT. We found that metoclopramide but not domperidone increased the phosphorylation state of phospholamban in the isolated perfused hearts or muscle strips of 5-HT4-TG, but not in WT. Metoclopramide, but not domperidone, shifted the positive inotropic or chronotropic effects of 5-HT in isolated left atrial and right atrial preparations from 5-HT4-TG dextrally, resp., to higher concentrations: the pEC50 of 5-HT for increase in force was in the absence of metoclopramide 8.6 ± 0.1 (n = 5) versus 8.0 ± 0.3 in the presence of 1 µM metoclopramide (n = 5; P < 0.05); and the beating rate was 7.8 ± 0.2 (n = 7) in the absence of metoclopramide versus 7.2 ± 0.1 in the presence of 1 µM metoclopramide (n = 6; P < 0.05). These results suggested that metoclopramide had an antagonistic effect on human cardiac 5-HT4 receptors. In summary, we showed that metoclopramide, but not domperidone, was a partial agonist at human cardiac 5-HT4-receptors.

Proarrhythmic potential of metoclopramide in a sensitive whole-heart model.

BACKGROUND: Metoclopramide (MCP) is a dopamine D2 -receptor antagonist, mainly used to treat post-operative or chemotherapy-induced nausea. While it is very effective in the cure of gastric symptoms, MCP can cause severe neurologic side effects. Furthermore, there is growing evidence for severe arrhythmic side effects resulting from inhibitory effects on cardiac sodium and potassium channels. METHODS AND RESULTS: Thirteen hearts of New Zealand white rabbits were retrogradely perfused, and electrophysiology studies were performed to obtain action potential duration (APD90 ) and effective refractory period (ERP). After generating baseline data, the hearts were perfused with increasing concentrations of metoclopramide (MCP 10 µM, MCP 50 µM, MCP 100 µM) and the standardized protocol was repeated for each concentration. Perfusion with MCP resulted in a significant prolongation of APD90 and QT interval. In parallel, the incidence of ventricular tachycardias was significantly increased by high doses of MCP. CONCLUSION: This is the first experimental study that investigated the effect of increasing doses of metoclopramide on a sensitive whole-heart model of proarrhythmia. MCP led to a significant increase in action potential duration and QT interval; meanwhile, the number of ventricular tachycardias was significantly increased.

Metoclopramide treatment blocks CD93-signaling-mediated self-renewal of chronic myeloid leukemia stem cells.

Self-renewal is a key characteristic of leukemia stem cells (LSCs) responsible for the development and maintenance of leukemia. In this study, we identify CD93 as an important regulator of self-renewal and proliferation of murine and human LSCs, but not hematopoietic stem cells (HSCs). The intracellular domain of CD93 promotes gene transcription via the transcriptional regulator SCY1-like pseudokinase 1 independently of ligation of the extracellular domain. In a drug library screen, we identify the anti-emetic agent metoclopramide as an efficient blocker of CD93 signaling. Metoclopramide treatment reduces murine and human LSCs in vitro and prolongs survival of chronic myeloid leukemia (CML) mice through downregulation of pathways related to stemness and proliferation in LSCs. Overall, these results identify CD93 signaling as an LSC-specific regulator of self-renewal and proliferation and a targetable pathway to eliminate LSCs in CML.

A Randomized, Double-Dummy, Emergency Department-Based Study of Greater Occipital Nerve Block With Bupivacaine vs Intravenous Metoclopramide for Treatment of Migraine.

BACKGROUND: Greater occipital nerve blocks (GONB) are used increasingly to treat acute migraine. OBJECTIVE: We conducted a randomized controlled trial to determine whether GONB was as effective as intravenous metoclopramide for migraine. METHODS: This was a double-dummy, double-blind, parallel-arm, non-inferiority study conducted in 2 emergency departments (EDs). Patients with migraine of moderate or severe intensity were randomized to receive bilateral GONB with each side administered 3 mL of bupivacaine 0.5% or metoclopramide 10 mg IV, the putative standard of care. The primary outcome was improvement in pain on a 0-10 scale between time 0 and 1 hour later. To reject the null hypothesis that metoclopramide would be more efficacious in relieving pain, we required that the lower limit of the 95% CI for the difference in pain improvement between those randomized to GONB vs those randomized to metoclopramide be >-1.3, a validated minimum clinically important difference. Secondary outcomes included sustained headache relief, defined as achieving and maintaining for 48 hours a headache level of mild or none without the use of additional analgesic medication, and the use of rescue medication in the ED. RESULTS: Over a 2.5-year study period, 1358 patients were screened for participation and 99 were randomized, 51 to GONB and 48 to metoclopramide. All of these patients were included in the primary analysis. Patients who received the GONB reported mean improvement of 5.0 (95% CI: 4.1, 5.8) while those who received metoclopramide reported a larger mean improvement of 6.1 (95% CI: 5.2, 6.9). The 95% CI for the between group difference of -1.1 was -2.3, 0.1. Sustained headache relief was reported by 11/51 (22%) GONB and 18/47 (38%) metoclopramide patients (95% CI for rounded difference of 17%: -1, 35%). Of the 51 GONB patients, 17 (33%) required rescue medication in the ED vs 8/48 (17%) metoclopramide patients (95% CI for rounded difference of 17%: 0, 33%). An adverse event was reported by 16/51 (31%) GONB patients and 18/48 (38%) metoclopramide patients (95% CI for (rounded) difference of 6%: -13, 25%). CONCLUSION: GONB with bupivacaine was not as efficacious as IV metoclopramide for the first-line treatment of migraine in the ED.

Methods and Success Factors of Induced Lactation: A Scoping Review.

BACKGROUND: Induced lactation enables a woman who has not given birth to breastfeed a child. Lactation may be induced through both pharmacological and non-pharmacological methods, although the desired outcome cannot always be achieved. RESEARCH AIMS: The aims of this scoping review was to assess the different methods used to induce lactation, as well as the factors related to sucking the breast effectively and the production of human milk. METHODS: We searched five databases from June 2019-February 2020 for studies referring to methods and factors related to breast suckling and/or the volume of milk produced after inducing lactation, using the following search terms and Boolean operators: breastfeeding AND induced lactation AND adoptive mothers OR surrogate mothers OR female homosexuality OR non-gestating. The final review included a total of 24 articles. RESULTS: Pharmacological methods were not always used to produce milk, although breast stimulation was essential. The age of the child, interference due to bottle feeding, breast stimulation, and the support received were important factors in the induction of lactation. There were several factors that may account for the differences between developing and higher income countries in methods of induced lactation and the amount of milk that study participants produced. There was no consensus over whether previous pregnancy and/or breastfeeding experience influenced induced lactation. CONCLUSION: Health professionals need to have adequate knowledge about induction methods, the preferences of each woman, and the reasons for inducing lactation, to provide proper assistance. However, the lack of standardization about induction of lactation makes it difficult.

Comparison of the Effects of Haloperidol, Metoclopramide, Dexmedetomidine and Ginger on Postoperative Nausea and Vomiting After Laparoscopic Cholecystectomy.

Nausea is a mental sensation of unease and discomfort before vomiting. Vomiting refers to the return of the contents of the upper gastrointestinal tract to the mouth caused by contractions of chest and abdomen muscles. Postoperative nausea and vomiting is an unpleasant experience with high treatment costs. Therefore, this study aimed to compare the effects of haloperidol, metoclopramide, dexmedetomidine, and ginger on postoperative nausea and vomiting after laparoscopy. This double-blind clinical trial was performed on all laparoscopy candidates at Valiasr hospital, Arak, Iran. The patients were randomly divided into four groups (haloperidol, metoclopramide, dexmedetomidine and ginger), and all patients underwent general anesthesia using fentanyl, midazolam, atracurium, and propofol. After intubation, tube fixation, and stable hemodynamic conditions, the patients received four ginger capsules with a hint of lemon. A group of patients received 25 µg of dexmedetomidine. In the Plasil group, 10 mg of metoclopramide was given 30 minutes before the completion of surgery. In addition, 0.5 cc of haloperidol (5 mg) was administered to a group of patients. Heart rate, blood pressure, and oxygen saturation were recorded from the beginning of surgery, every 15 minutes until the end of the surgery. Furthermore, the occurrence of nausea and vomiting was recorded during recovery, 2 and 4 hours after surgery. Data were then analyzed using the SPSS software v.23. Eighty-eight patients were enrolled in the study. The youngest and the oldest were 30 years and 70 years old, respectively, and the mean age was 48.02 ± 9.31 years. Moreover, the number of women in the four groups was higher than that of men. Blood pressure in the dexmedetomidine group was lower than the other four groups (P <0.05). The lowest heart rate was observed in the haloperidol group, while the highest heart rate was seen in the plasil group (P <0.05). The occurrence of vomiting and nausea was not significantly different between the four groups (P <0.05). Our results showed no significant difference in postoperative nausea and vomiting between the four drugs. Due to the hemodynamic changes induced by each drug, it is best to use these drugs based on the patient's condition. Ginger is also a herbal remedy that has fewer side effects, and this drug can be a good option for patients when there is no contraindication.

Ultrasonographic assessment of the effect of metoclopramide, erythromycin, and exenatide on solid-phase gastric emptying in healthy cats.

BACKGROUND: Available data on the effect of gastrointestinal motility-modifying drugs in cats are limited. Most recommendations for drug usage and dosage are based on collective clinical experience. OBJECTIVES: To assess the effects of metoclopramide, erythromycin, and exenatide on gastric emptying (GE) and gastric motility in comparison to placebo. We hypothesized that metoclopramide and erythromycin would have prokinetic gastric effects, whereas exenatide would prolong GE times and decrease the motility index (MI) of antral contractions. ANIMALS: Eight healthy domestic shorthair cats. METHODS: Each cat had 4 separate ultrasonographic assessments. In a prospective, randomized, double-blind, 4-way crossover design, cats received placebo, metoclopramide, erythromycin, or exenatide for 2 days followed by a minimum 5-day washout period. Ultrasonographic GE times and MI were compared to placebo. RESULTS: When compared to placebo, the rate of GE was significantly faster after administration of metoclopramide and erythromycin. Significant differences were found at all fractions of GE after administration of erythromycin and all but 1 fraction after metoclopramide when compared to placebo. The rate of GE in the first half of the GE curve was significantly slower after exenatide administration. The total area under the Ml curve was significantly larger after administration of metoclopramide and erythromycin than after placebo. CONCLUSIONS AND CLINICAL IMPORTANCE: Metoclopramide and erythromycin shorten GE times and increase the MI of antral contractions, thus having a prokinetic effect in the stomach of healthy cats, whereas exenatide causes an initial delay in GE.

Metoclopramide use to induce lactation can alter DRD2 and BDNF in the prefrontal cortex of offspring.

Metoclopramide, used as an anti-emetic drug in clinical practice, has recently also begun being used to establish hyperprolactinemic effects in breastfeeding. The purpose of this study was to investigate the potential side-effects of metoclopramide applied in the lactation period in the central nervous system of offspring rats. Eighteen female albino Wistar rats that had just given birth were divided into three groups together with their pups, healthy controls, low-dose metoclopramide (10 mg/kg, twice per day i.p.) and a high-dose metoclopramide group (45 mg/kg, twice per day i.p.). Brain tissues from six pups from each mother were harvested at the end of the 21st day. Immunohistochemical and ELISA techniques were performed using dopamine D2 receptor (DRD2), brain derived neurotrophic factor (BDNF) and neural growth factor (NGF), markers of extrapyramidal reaction in the brain, as signal molecules. Based on biochemical levels and immunohistochemical results, DRD2 expression decreased only in the external pyramidal layer neurons in the high-dose offspring group. Strong BDNF reaction was determined in pyramidal neurons in all layers in the control offspring group, and decreased reaction was observed in the high- and low-dose groups. No significant difference was observed in NGF expression between the three groups. Since high-dose metoclopramide caused a decrease in DRD2 expression in the external pyramidal layer in the prefrontal cortex, and since both high and low doses reduced BDNF expression, care needs to be taken with the use of metoclopramide in the lactation period due to the possibility of extrapyramidal reactions in offsprings.