Glucocorticoids attenuate taste aversions produced by toxins in rats

Conditioned taste aversions (CTAs) develop if toxicosis is induced after an animal eats or drinks. Usually, if a second drug is administered after consumption and prior to the toxin, it either adds to the CTA produced by the toxin or else has no noticeable effect. However, glucocorticoids (dexamethasone, cortisol, methylprednisolone, and prednisolone) attenuate CTAs produced by cyclophosphamide. Dexamethasone was tested most extensively and is also effective against CTAs produced by carmustine, cisplatin, copper sulfate, cytarabine, dactinomycin, doxorubicin, lithium chloride, and mechlorethamine. Delta-9 THC, domperidone, haloperidol, metoclopramide, and scopolamine were ineffective against CTAs produced by cyclophosphamide, although they are used medically for palliative purposes. Prochlorperazine attenuated CTAs but to a much smaller extent than the glucocorticoids. These results are interpreted as cross-validation of recent reports that glucocorticoids alleviate clinically observed distress produced by cancer chemotherapies.     

甲氧氯普胺液相中球型结聚微丸的制备及特性考察

采用液相中药物球型结聚技术制备了甲氧氯普胺微丸，并对产品的特性进行了考察。结果表明，产品成形性好，不同批号的产品及同一批号不同粒径的产品主药含量基本一致。微丸具有一定的缓释作用，溶出速率主要决定于乙基纤维素用量及产品粒径大小。制备过程中，甲氧氯普胺与乙基纤维素间可能形成了氢键结合。     

Bioavailability studies with ciglitazone in beagles II. Effect of propantheline bromide and metoclopramide HCL on bioavailability of a tablet

Bioavailability studies in fasted dogs with ciglitazone (CGZ), an oral hypoglycemic agent, suggested that an absorption window could contribute to the poor oral availability of CGZ. If so, propantheline bromide (PPB) could increase the residence time of CGZ at absorption sites and increase its bioavailability. Using this rationale, a Latin square study was conducted with CGZ in fasted dogs (n = 10) using treatments of a single 125mg tablet with and without 1.2 mg kg⁻¹ i.m. PPB. PPB was given in a single dose 1 h prior to administration of CGZ. Plasma concentrations of CGZ were assayed by HPLC. PPB significantly increased the AUC of CGZ by a ratio of 1.2 : 1 (p < 0.01). PPB also increased T_max from 2–8 h (p<0.001), and appeared to produce first order absorption of CGZ. In a separate CGZ study using fasted dogs (n = 10), a single 125mg tablet was administered with and without i.v. metoclopramide HCI (MCP). A 10mg dose of MCP was given 15 min prior to dosing with CGZ and repeated 1 h after dosing. MCP increases GI motility and was expected to decrease residence time of CGZ. MCP had no effect on T_max, but significantly decreased AUC by 8 per cent (p = 0.05). MCP also reduced C_max by 16 per cent (p = 0.06). Taken as a whole, these data suggest that the effect of meals to increase bioavailability of CGZ could be mediated at least in part, through an increase in GI residence time.     

Comparison of the efficacy and side-effects of ondansetron and metoclopramide-diphenhydramine administered to control nausea and vomiting in children treated with antineoplastic chemotherapy: a prospective randomized study

Nausea and vomiting following antineoplastic therapy in patients receiving chemotherapy remains a problem. To prevent nausea and vomiting due to antineoplastic therapy, many types of drugs have been used. Ondansetron and the combination metoclopramide-diphenhydramine have been widely used in children. In this prospective randomized study these drugs were compared both for their efficacy and side-effects in children treated with antineoplastic chemotherapy (with and without cisplatin) the number of chemotherapy courses being equal in both groups. Ondansetron gave complete anti-emetic cover in five of nine courses in patients treated with cisplatin. Metoclopramide-diphenhydramine gave complete anti-emetic cover in one out of nine courses, and 17 out of 23 courses in patients treated without cisplatin. Metoclopramide-diphenhydramine produced side effects in nine courses whereas ondansetron produced side-effects in three courses. Conclusion Ondansetron appeared to be superior to metoclopramide-diphenhydramine in the control of emesis induced by chemotherapy regimens containing cisplatin. The results of the present prospective randomized study indicate that ondansetron is a useful anti-emetic in the treatment of chemotherapy-induced emesis. Received: 17 May 1996 / Accepted in revised form: 23 December 1997     

Response decrement patterns after neuroleptic and non-neuroleptic drugs

Previous work has shown that administration of pimozide and other neuroleptic drugs can produce within-session response decrement patterns of appetitively-reinforced behaviour. This phenomenon has been described as an extinction-like pattern of responding and used as evidence for the hypothesis that these drugs attenuate the rewarding properties of food, water and electrical stimulation of the brain. The present study was carried out to investigate within-session patterns of responding maintained by food presentation or shock avoidance after administration of a variety of neuroleptic and non-neuroleptic drugs. Haloperidol, metoclopramide, pimozide and butaclamol produced within-session response decrements of both food-reinforced lever pressing and one-way shock avoidance. The atypical antipsychotic drug clozapine did not consistently produce similar effects nor did the -adrenoceptor agonist clonidine, the opiate agonist morphine, the benzodiazepine anxiolytic chlordiazepoxide and the muscle relaxant methocarbamol, although all these drugs were tested up to doses which markedly disrupted responding. Thus, within-session response decrement patterns are a characteristic effect of dopamine-blocking neuroleptic drugs. However, because of the generally similar effects of these drugs on appetitively-and aversively-motivated behaviour, these effects are probably best interpreted as actions on motor, rather than motivational, mechanisms.     

Premedication with metoclopramide decreases the frequency of methohexital induced hiccup

Metoclopramide is one of many drugs that have been recommended for the treatment of intractable hiccup. Methohexital may produce hiccup during induction of general anesthesia. 211 women received methohexital for induction and maintenance of general anesthesia for short gynaecological procedures. All the patients were premedicated with fentanyl, diazepam and atropine. 109 patients were randomly selected to receive metoclopramide before induction of anesthesia; the remaining 102 patients served as a control group, and were anesthetized without metoclopramide premedication. The frequency of hiccup was compared between the two groups. 7 patients had hiccup in the metoclopramide premedicated group, as compared to 17 patients in the control group. This difference was statistically significant. We conclude that metoclopramide reduces the frequency of methohexital induced hiccup, and recommend that metoclopramide be routinely used for the premedication of methohexital injection.(Stav A, Weksler N, Berman M: premedication with metcoclopramide decreases the frequency of methohexital induced hiccup. J Anesth 6: 17–20, 1992)     

Vasopressin, prolactin and growth hormone in Alzheimer's disease: their evaluation after metoclopramide stimulation

Recent studies have shown that there is a relationship between an alteration of central neurotransmitters and the modification of some biohumoral parameters in Alzheimer's Disease (AD).

In this study the authors evaluated, after metoclopramide (MTC) stimulation, the concentration curve of vasopressin (AVP), prolactin (PRL) and growth hormone (HGH) in the plasma of 34 subjects (20 males and 14 females, mean age 70.5±6.9 years; 17 were AD patients, the others constituted the control group). MTC increased AVP serum concentration in healthy (P <0.001), but not in AD patients. This result seemed to be due to the lack of ‘procholinergic’ action of the drug in the AD patients probably due to an alteration in their cholinergic pathways. The PRL response to MTC was reduced only in the AD female group (P <0.005), suggesting an alteration in dopaminergic control. Lastly, the HGH response in AD did not differ in the two groups, neither in basal conditions, nor after MTC stimulation. The absence of HGH response both in AD and in healthy subjects, demonstrated the ineffectiveness of MTC stimulation.

We can conclude that AVP and PRL responses to MTC stimulation efficiently separated the two groups (AD and controls); the former test showing a higher discriminant power than the latter.     

胃复安治疗急性感染性腹痛腹泻的临床疗效观察

目的观察胃复安治疗急性感染性腹痛腹泻的临床疗效。方法将涞源县医院2010年3月-2011年5月收治的84例急性感染性腹痛腹泻患者，遵照知情同意原则并按照随机数字表法随机分为两组，对照组42例患者采用常规治疗方法，观察组42例患者在常规治疗基础上加用胃复安治疗，比较分析两组的临床疗效。结果观察组总有效率为97．6％，对照组为81．0％，两组间差异有统计学意义（X2=4．48，P〈0．05），两组均无明显不良反应发生。结论胃复安治疗急性感染性腹痛腹泻疗效满意，且安全性好，是临床首选的治疗药物之一。     

食管心房调搏前肌注胃复安注射液对电极安放耗时和安全性的影响

目的：评价食管心房调搏前肌内注射胃复安注射液对电极安放耗时和安全性的影响。方法选择2012年2月至2013年5于泸州市中医医院心血管内科门诊行食管心房调搏检查的患者80例,依据计算机软件编制随机分配表将患者分为试验组42例和对照组38例,两组均于食管心房调搏前肌内注射药物1 mL（试验组为胃复安注射液1 mL／10 mg,对照组为0．9％氯化钠注射液1 mL,两组均为无色透明液体）,观察经鼻食管电极安放平均耗时及安全性（误吸及恶心呕吐）。结果试验组电极安放平均耗时较对照组显著缩短,差异有统计学意义（P ＜0．05）;试验组患者0例出现误吸,对照组患者1例,差异无统计学意义（P＞0．05）;恶心呕吐评级比较,试验组安全性优于对照组（P＜0．05）。结论在食管心房调搏前肌注胃复安注射液能明显缩短电极安放耗时,提高电极安放的安全性,减轻患者痛苦。     

Sustained release microspheres of metoclopramide using poly(D,L-lactide-co-glycolide) copolymers

Metoclopramide was encapsulated with poly(D,L-lactide co glycolide) copolymers of different molecular weights using the emulsification/solvent evaporation technique. These polymers included poly(D,L-lactide-co-glycolide) 50:50 with inherent viscosity (i.v.) 0.2, and average molecular weight 8000, poly(D,Llactide-co-glycolide) 50:50 with i.v. 0.8 and average molecular weight 98000 and poly(D,L-lactide-co-glycolide) 85:15 with i.v. 1.4 and average molecular weight 220000. The effect of the polymers' molecular weights as well as the polymer-to-drug ratios on the yield, the particle size distribution, and the drug content of the microspheres was investigated. The release rate of the drug was studied for 96h in a phosphate buffer of pH7.4. The study also investigated the effect of the new poly(lactide-co-glycolide)-H series on the characteristics of the prepared microspheres. Data revealed that a higher yield was obtained with polymers of lower molecular weights. A lower yield was also obtained with increasing the drug-to-polymer ratios for all the investigated polymers. The drug content of the microspheres was lower than expected, ranging from 49-85%, which suggested a chemical interaction between the drug and the polymers, as proved by differential scanning calorimetry (DSC) and infra red (IR) studies. A higher interaction was obtained with the H-series of the copolymers. The release of the drug mainly followed zero order kinetics on increasing either the polymers' molecular weights or the polymer-to-drug ratios. Diffusion kinetics was observed only with those batches prepared with low polymer-to-drug ratios. The release rate was a function of both the polymers' molecular weights and the drug-to-polymer ratios.