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PubMed1986

Enhancement of the antiemetic action of metoclopramide against cisplatin-induced emesis by transdermal electrical nerve stimulation.

In a double-blind sequential trial, the influence of transdermal electrical nerve stimulation (TENS) was studied in patients who were treated with total infusions of metoclopramide 3.5 mg/kg to counter the emetic action of cisplatin 60-90 mg/m2. Transdermal electrical nerve stimulation further reduced the emetic episodes in ten of 11 treatment pairs (2 alpha = .10). This effect was blocked by naloxone. More surprisingly, TENS reduced the incidence of extrapyramidal effects of metoclopramide (i.e., akathisia and dystonia). These effects may be explained by the involvement of central nervous and peripheral TENS-induced production of opioid neuromodulators. An alternate hypothesis is the stimulation of serotonergic mechanisms via neuromodulation by opioid peptides, or by involvement of both systems.

Adult↗

PubMed1994

Effect of zatosetron on ipecac-induced emesis in dogs and healthy men.

Serotonin receptor (5-HT3) antagonists provide effective antiemetic therapy in cancer patients receiving emetogenic chemotherapy, such as cisplatin. Animal studies have shown that 5-HT3 receptor antagonists also have antiemetic activity in ipecac-induced emesis. The authors investigated the antiemetic activity of zatosetron maleate, a 5-HT3 receptor antagonist, on ipecac-induced emesis in dogs and healthy men. They also evaluated the effect of ipecac administration on serotonin release and metabolism by measuring urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion in healthy men. In separate randomized, placebo-controlled trials, 20 dogs received zatosetron intravenously and eight healthy men received zatosetron (50 mg) orally, followed by ipecac syrup. In both trials, emetic response to ipecac was recorded, including the number and time of vomits and retches. Zatosetron treatment inhibited and delayed ipecac-induced emesis in both groups. In dogs, zatosetron inhibited ipecac-induced emesis in a dose-dependent manner with a 100-micrograms/kg dose producing complete inhibition. In men, zatosetron administration resulted in fewer emetic episodes after ipecac than had occurred with placebo administration (P = .03); vomiting was completely inhibited by zatosetron. In men, ipecac administration did not affect the urinary 5-HIAA/creatinine ratio (mg/g) or 5-HIAA excretion rate (microgram/hour). Our study demonstrates that zatosetron has similar efficacy on ipecac-induced emesis in healthy men, as has been shown previously with other 5-HT3 receptor antagonists in chemotherapy-induced emesis in cancer patients. We did not observe the increase of urinary 5-HIAA in our study with ipecac-induced emesis, however, as has been described previously in cisplatin-induced emesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMedDate not supplied

Adrenal corticosteroids as antiemetics during cancer chemotherapy.

Adrenal corticosteroids were first reported in 1979 to have antiemetic effects during cancer chemotherapy. Since then considerable numbers of trials have been conducted to evaluate their activity alone and in combination with other agents. The majority of the research has centered on dexamethasone, although other corticosteroids have been studied. Dexamethasone as a single agent is superior to placebo and appears to be more effective than standard doses of prochlorperazine when administered with highly emetic agents. Dexamethasone is comparable to metoclopramide against moderately emetogenic agents and low-dose cisplatin, but less effective than metoclopramide against highly emetic agents or high-dose cisplatin. Dexamethasone improves the activity of prochlorperazine and metoclopramide and may reduce some of the side effects associated with the latter. Current trials continue to explore the role of corticosteroids alone and in combination with antiemetics.

Antineoplastic Agents↗

PubMed1986

Clinical evaluation of the simultaneous blockade of the dopamine D-2, histamine H-1, and muscarinic cholinergic receptors in cancer chemotherapy-induced emesis: results of a controlled trial.

Twenty-six patients being treated with 5-fluorouracil-adriamycin-cyclophosphamide (FAC), or vincristine-adriamycin-cyclophosphamide (VAC) chemotherapy completed a randomized, double-blind, cross-over study in which the antiemetic activity of thiethylperazine (6.5 mg p.o. every 8 h X 5 days) was compared with that of the combination of thiethylperazine (same dosage) plus amitriptyline (25 mg p.o. every 8 h X 5 days). This combination was designed to obtain a simultaneous blockade of the dopamine D-2, histamine H-1, and muscarinic cholinergic receptors of the central structures responsible for emesis (chemoreceptor trigger zone and vomiting center). The combination significantly decreased both the number of emetic episodes (P less than 0.05) and the duration of emesis (P less than 0.01) compared with thiethylperazine alone. The combination was also preferred by a significantly higher number of the patients (P less than 0.001) who were exposed to both the types of antiemetic treatment under trial. The combination of thiethylperazine plus amitriptyline was shown to have a satisfactory antiemetic activity against vomiting induced by VAC chemotherapy in males; it afforded major protection (two emetic episodes or fewer) in 83% of the cases. Nonetheless, it cannot be considered a satisfactory treatment for the control of vomiting induced by FAC chemotherapy in female patients, only 43% of whom achieved major antiemetic protection.

Aged↗

PubMed1986

An effective five-drug antiemetic combination for prevention of chemotherapy-related nausea and vomiting. Experience in eighty-four patients.

Antiemetics of known efficacy have been shown to block mainly one of three neurotransmitter receptors in the brain. A combination of antiemetics, designed specifically for outpatient use and consisting of metoclopramide, thiethylperazine, diphenhydramine, dexamethasone, and diazepam, is capable of blocking multiple sites in the emesis pathway. Eighty-four patients receiving highly emetic chemotherapy (85% received cisplatin) completed 200 trials of this five-drug combination using two similar regimens. Complete control (i.e., no nausea or vomiting) was achieved in 45% and two or fewer episodes of vomiting was experienced in 72% of these 200 trials. The mean number of vomiting episodes was 1.65, the median 1.0, and the range 0-15. Sedation was nearly universal, although no serious toxicity was encountered. Thus, this antiemetic combination designed for outpatient use proved highly effective in controlling nausea and vomiting associated with highly emetic anticancer treatment.

Adolescent↗

PubMed1994

Efficacy and tolerability of nasally administered compared to parenterally administered metoclopramide in the symptomatic treatment of chemotherapy-induced emesis in cancer outpatients. A controlled clinical study.

The clinical efficacy and tolerability of a new nasal spray formulation of metoclopramide (MTC) was evaluated in terms of its ability to prevent the nausea and vomiting induced by a moderately emetic chemotherapy (cisplatin 20 mg/m2 weekly as radioenhancer+radiotherapy for a fractionated total of 60 Gy) in 12 patients with non-small-cell lung cancer, stage IIIB. The first chemotherapy cycle was administered without any prophylaxis in order to identify those patients who experienced grade 2 nausea and/or vomiting. As prophylaxis during the second cycle, these patients were given MTC 20 mg i.v. at time zero, and MTC 20 mg i.m. after 4 h and 8 h; during the third cycle, they received MTC 40 mg by nasal spray 2 h before chemotherapy, followed by the same dose at 4 h and 8 h. The two prophylactic treatments (parenteral injections and nasal spray) proved to be therapeutically equivalent: complete protection, 6 and 6 patients respectively; major protection, 2 and 3 patients; minor protection, 1 and 1 patient; no protection, 3 and 2 patients. The control of nausea was satisfactory, with 7 and 9 patients respectively experiencing grade 0-1 nausea. Comparative analysis of individual responses confirmed the similar anti-emetic efficacy of the two regimens. No adverse reactions were observed at any time during the course of the study, and all 12 patients judged the acceptability of the new formulation as optimal. It can thus be concluded that the use of metoclopramide nasal spray represents an effective, safe, easily managed and low-cost therapeutic alternative for the prophylaxis and treatment of emesis induced by low-dose chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

PubMed1991

Antiemetic activity of the new 5-HT3 antagonist DAU 6215 in animal models of cancer chemotherapy and radiation.

The antiemetic activity of DAU 6215, a novel antagonist of 5-HT3 receptors, was investigated in animal models of cytotoxic treatment-evoked emesis and compared with the antiemetic activity of ondansetron and metoclopramide. In dogs, vomiting was induced by i.v. cisplatin; in ferrets, the emetic response was elicited by i.v. doxorubicin or X-ray exposure. Pretreatment with 0.1-1 mg/kg DAU 6215 given i.v. or p.o. prevented the vomiting response to the different emetic agents. In the dog, the antiemetic potency of metoclopramide was 30 times lower than that of DAU 6215. Ondansetron was less potent than DAU 6215 against cisplatin and doxorubicin but was equally effective in the radiotherapy protocol. In this model, lengthening of the pretreatment time to 2 h did not affect the antiemetic efficacy of DAU 6215, whereas it decreased that of ondansetron. The results demonstrate that DAU 6215 is a highly effective and long-lasting inhibitor of cytotoxic treatment-induced emesis in different animal species.

Animals↗

PubMed1983

Responses of neurons of canine area postrema to neurotransmitters and peptides.

The responses of 122 neurons in the area postrema of anesthetized dogs to 17 common transmitters and peptides were determined. Recordings were made from one barrel of a seven-barrel ionophoretic electrode. All neurons were silent at rest, but most could be detected and excited by the application of glutamate. The glutamate response was a brief, high-frequency response of less than 1-sec duration. Excitatory responses were also found to histamine, norepinephrine, serotonin, dopamine, apomorphine, angiotensin II, neurotensin, leucine enkephalin, vasoactive intestinal polypeptide, thyrotropin releasing hormone, gastrin, vasopressin, and substance P. While most neurons tested were excited by dopamine and apomorphine, approximately half of those studied were also excited by each of the other substances. Inhibitory responses were found to norepinephrine (6 of 15 cells) and histamine (3 of 45 cells). No responses were found to acetylcholine, somatostatin, or cholecystokinin. The responses to all 13 excitatory substances other than glutamate were similar. Typically these responses had a latency of 2-20 sec and lasted for 30 sec to 5 min on their first application. The frequency of discharge was usually low (approximately 0.5 Hz). Multiple applications of these agents often induced a maintained spontaneous discharge of low frequency. Each application also induced a transient incremental discharge at a frequency that rarely exceeded 2 Hz. The area postrema has been proposed to be the "chemoreceptor trigger zone" for emesis (Borison and Wang, 1953). All of the agents which excite area postrema neurons, with the exception of serotonin and norepinephrine, are emetic, while none of the three agents without excitatory effects is known to be emetic. Thus these results provide strong support for the central role of the area postrema in emesis. The similarity of response to so many substances on small neurons suggests a common ionic and/or metabolic mechanism underlying the response. The prolonged nature of the response to brief administration of these agents would seem to be appropriate for neurons which subserve a sensation and behavior such as nausea and vomiting.

Action Potentials↗

PubMed1976

Therapeutical efficacy of a combination of apomorphine with sulpiride or metoclopramide in Parkinsonism.

In healthy volunteers the emetic effect of apomorphine (5-10 mg, i.m.) was prevented by haloperidol (2 mg), metoclopramide (10 mg) and sulpiride (100 mg), injected intramuscularly. In parkinsonian patients, apomorphine (1 mg) given alone ameliorated the neurological symptoms (30% improvement in the disability score), but the improvement was accompanied by nausea, vomiting, sedation or sleepiness. Haloperidol (2 mg) prevented not only the emetic effect of apomorphine (10 mg), but also its therapeutic efficacy in parkinsonism. Indeed, the disability score was worsened by the drug combination in some patients. Moreover, after haloperidol, apomorphine produced deep sedation and sleep. By contrast, in parkinsonian patients pretreated with metoclopramide (10 mg) or sulpiride (100 mg), apomorphine (10 mg) markedly diminished tremor and rigidity and failed to produce nausea, vomiting and sleepiness.

Adult↗

PubMed1991

5-HT3 receptor antagonists and migraine therapy.

Neuronal 5-hydroxytryptamine3 (5-HT3) receptors mediate the excitatory effects of 5-HT. They are located in pain- and nausea-modulating areas in the central nervous system and on C-fibre primary afferents in the peripheral nervous system. Consequently, these receptors mediate the painful and emetic effects of 5-HT. Selective and potent 5-HT3 receptor antagonists have been shown to block inflammatory and 5-HT induced and potentiated "vascular pain". Based on the hypothesis that 5-HT3 receptor antagonists may block neurogenic dural inflammation in the distribution area of the trigeminal nerve and, thus, could potentially prevent migraine (pain), four highly selective and potent 5-HT3 receptor antagonists have been tested in both the acute and prophylactic treatment of migraine. Unfortunately, except for a clear anti-emetic effect, none of these drugs has shown unequivocal efficacy in the treatment of migraine. This may be partly due to the complex (bell-shaped) dose-response relationship of these compounds, making exact titration of the correct dose difficult. Moreover, most 5-HT3 receptor antagonists have proved to be toxic in man on chronic administration thereby preventing further trials in migraine with adjusted doses. Short-term treatment for cytotoxic drug-induced emesis so far appears to be the only proven indication for 5-HT3 receptor antagonists.

Humans↗

PubMed1985

[Benefit and risk of high-dose metoclopramide in comparison to high-dose haloperidol or triflupromazine in cisplatin-induced vomiting].

The antiemetic efficacy of metoclopramide (MCL, Paspertin, loading infusion 0.5 mg/kg body wt./h over 2 h, maintenance infusion 0.25 mg/kg/h over 24 h) has been compared with haloperidol (HAL, Haldol, 1/10 of MCL dosage) and with triflupromazine (TFP, Psyquil, 1/2 of MCL dosage) in two sequential analyses, against the emetic effects of cisplatin (60-90 mg/m2). After treating 14 and 8 pairs of patients respectively, MCL was significantly (alpha = 0.05) more effective than HAL or TFP. Only 1 of the 14 patients in the HAL group and 0 of 8 in the TFP group were totally protected against emesis, in contrast to 6 of 14 patients and 3 of 8 in the MCL groups. In order to quantify the benefit/risk relationship of the antiemetic drugs studied the number of prevented emetic episodes (in comparison to previous insufficient treatment) was related to the incidence of major undesired effects (i.e. dystonia and/or akathisia). This relationship was 17.8 and 12.1 for the two MCL groups; for HAL and TFP it was only 5.8 and 4.6, respectively. The high antiemetic selectivity of MCL against cisplatin-induced emesis is probably related to the still unknown action of MCL on the gastrointestinal motility. A high neuroleptic potency, with or without additional anticholinergic activity, is apparently not essential for high antiemetic protection against cisplatin.

Cisplatin↗

PubMed1991

Pathophysiology of cytotoxic drug-induced emesis: far from crystal-clear.

Both radiotherapy and chemotherapy for cancer are capable of causing severe nausea and vomiting, which formerly often interfered with the patient's compliance to treatment. The basic pathway and pharmacological mechanisms involved in this are still poorly understood. The recent discovery, however, that 5-HT3 receptor antagonists can prevent or greatly reduce chemotherapy-induced emesis led to a re-evaluation of the sequence of events occurring in the protective emetic reflex, which are reviewed in this paper. The vomiting centre co-ordinates the incoming and outgoing information, and is thought to be represented by complex interactions between different adjacent areas in the brainstem. Whether the main role in the emetic reflex arch is accomplished by either the central part (chemoreceptor trigger zone) or the peripheral part (gastro-intestinal tract) needs further confirmation A more important role, however, of the vagal nerve and the gastro-intestinal tract is generally accepted. The neurotransmitter serotonin (5-HT) appears to play a major role in chemotherapy-induced emesis via the 5-HT receptor. These indications could form the basis for further investigations into the involvement of other neurotransmitters, and the character of their interactions.

Animals↗

PubMed1998

Preoperative education and outcome of patient controlled analgesia.

PURPOSE: To determine the effect of intensive preoperative education on the outcome of Patient Controlled Analgesia (PCA) postoperatively. METHODS: This prospective randomised study was carried out in a single teaching hospital over three months. One group of patients (n = 42) received a 20 min standardised tutorial regarding PCA use from a single investigator and the other group (n = 43) received no additional education apart from the routine preoperative anaesthetic consultation. A blinded investigator assessed the patients following surgery. Pain scores and morphine consumption, patient satisfaction, side-effect profile and anti-emetic use were recorded at six, 24 and 48 hr postoperatively. RESULTS: Pain scores, satisfaction scores and morphine consumption were similar in both groups throughout the study period. Fewer patients in the tutored group complained of nausea from 6 to 24 hr than did untutored patients (28% vs 51%; P < 0.05). More tutored patients used antiemetic medication from 0 to 6 (28% vs 12%; P < 0.05) and 6 to 24 hr (37% vs 19%; P < 0.05). Side effect profile and requirement for rescue analgesia was otherwise similar in both groups. CONCLUSION: Our results suggest that specific preoperative education of patients using PCA does not alter pain scores, morphine consumption or patient satisfaction but may result in earlier and more effective use of anti-emetic medication.

Analgesia, Patient-Controlled↗

PubMed1997

Intravenous dolasetron mesilate ameliorates postoperative nausea and vomiting.

PURPOSE: To compare the efficacy, safety, and tolerability of dolasetron mesilate with placebo for the treatment of postoperative nausea and vomiting (PONV). METHODS: In a randomized, multicentre, double-blind, placebo-controlled study 337 adult patients undergoing surgery with general anaesthesia received one of four single, doses of dolasetron mesilate iv (12.5, 25, 50, or 100 mg) or placebo. Study medication was administered postoperatively when the patient reported nausea lasting 10 min or when one emetic episode occurred within two hours of the patient's arrival in the recovery room. Efficacy was assessed by the investigators over the 24-hr study period by recording the number and timing of emetic episodes, the severity of nausea, the timing of administration of escape antiemetic medications, and patients' and investigators' satisfaction with antiemetic therapy. RESULTS: The study sample was predominately women, and the surgical procedures were primarily gynaecological. All dolasetron mesilate doses produced higher complete response rates than placebo (P < 0.05). Only approximately one-third of dolasetron patients required escape antiemetic medication compared with more than 50% of patients in the placebo group. Both patient and physician satisfaction with dolasetron treatment was high. The most common adverse event was mild or moderate headache for both placebo-treated patients and dolasetron-treated patients. Clinical laboratory results were unremarkable. CONCLUSION: Single doses of dolasetron mesilate iv, given after the first episode of PONV, were both effective and safe in this adult patient population.

Adolescent↗

PubMed1997

Comparison of tramadol and tramadol/droperidol mixture for patient-controlled analgesia.

PURPOSE: To compare the analgesic efficacy and side effects of tramadol vs tramadol and droperidol for post-operative patient-controlled analgesia (PCA). METHODS: Randomised, double-blind study. Thirty-four patients undergoing elective colorectal or head and neck surgery were allocated to Group 1 (n = 18, PCA bolus 10 mg tramadol) or Group 2 (n = 16, PCA bolus 10 mg tramadol + 0.1 mg droperidol). Anaesthesia was induced with fentanyl and thiopentone and maintained with O2, N2O plus enflurane or isoflurane with iv morphine at doses decided by the attending anaesthetists. Muscle relaxation was achieved with atracurium or vecuronium. Patients were observed four-hourly for pain using an 11-point verbal rating scale (VRS). Nausea and vomiting, and sedation were assessed using four-point scales post-operatively. Vital signs, request for rescue anti-emetic and analgesic, and overall satisfaction were recorded. RESULTS: The mean nausea scores were lower in Group 2 (1.00 +/- 1.33 vs 0.06 +/- 0.25 at 0-8 hr, 1.22 +/- 1.93 vs 0.06 +/- 0.25 at 8-16 hr, P < 0.01; 0.81 +/- 1.68 vs 0 at 32-40 hr, P < 0.05; Group 1 vs Group 2). The vomiting scores were also lower (0.50 +/- 1.04 vs 0 at 0-8 hr, 0.67 +/- 1.50 vs 0, at 8-16 hr, P < 0.05; Group 1 vs Group 2). Seven (39%) patients in Group 1, but none in Group 2 requested rescue anti-emetic (P < 0.01). There were no differences in VRS, sedation score, overall satisfaction or vital signs. CONCLUSION: Tramadol and droperidol combination is superior to tramadol alone for post-operative PCA. It provides a similar quality of analgesia with less nausea and vomiting and without an increase in sedation.

Adult↗

PubMed2004

A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew).

RATIONALE: The 5-HT3 antagonist, ondansetron (OND), and the cannabinoid, delta9-tetrahydrocannabinol (delta9-THC), have been shown to interfere with emesis; however, their relative and/or combined effectiveness in suppressing vomiting produced by the chemotherapeutic agent, cisplatin, is unknown. OBJECTIVE: To evaluate the potential of: 1) a broad range of doses of delta9-THC and OND to prevent cisplatin-induced vomiting and retching in the Suncus murinus (house musk shrew), 2) combined treatment with ineffective individual doses of delta9-THC and OND to prevent cisplatin-induced vomiting and retching, 3) the CB1 receptor antagonist, SR141716, to reverse the antiemetic effects of OND, and 4) cannabidiol (CBD), the principal non-psychoactive component of marijuana, to reverse cisplatin-induced vomiting in the shrew. METHODS: Shrews were injected with various doses of OND (0.02-6.0 mg/kg), delta9-THC (1.25-10 mg/kg) and a combination of ineffective doses of each (0.02 mg/kg OND+1.25 mg/kg delta9-THC) prior to being injected with cisplatin (20 mg/kg) which induces vomiting. Shrews were also injected with CBD (5 mg/kg and 40 mg/kg) prior to an injection of cisplatin. RESULTS: OND and delta9-THC both dose-dependently suppressed cisplatin-induced vomiting and retching. Furthermore, a combined pretreatment of doses of the two drugs that were ineffective alone completely suppressed vomiting and retching. CBD produced a biphasic effect, suppressing vomiting at 5 mg/kg and potentiating it at 40 mg/kg. CONCLUSIONS: A low dose of the non-intoxicating cannabinoid CBD may be an effective anti-emetic treatment and combined doses of OND and delta9-THC that are ineffective alone suppresses cisplatin-induced emetic reactions in shrews.

Animals↗

PubMed2000

The 5-HT3 agent N-(3-chlorophenyl)guanidine (MD-354) serves as a discriminative stimulus in rats and displays partial agonist character in a shrew emesis assay.

RATIONALE: There is some, albeit conflicting, evidence that 5-HT3 receptors might be involved in the actions of abused stimulants. Most studies have focussed on examinations of 5-HT3 antagonists; this might be due to a lack of high-affinity 5-HT3 agonists that readily penetrate the blood-brain barrier. OBJECTIVES: N-(3-Chlorophenyl) guanidine (MD-354) is a member of a novel class of 5-HT3 ligands developed in our laboratories. We have previously demonstrated that MD-354 can exert agonist effects and now further explore this action. METHODS: Rats (n=9) were trained to discriminate 2 mg/kg MD-354 from saline vehicle in a two-lever drug discrimination task (VI-15 s schedule of reinforcement). The actions of agents with 5-HT3 character were evaluated. The emetic and antiemetic actions of MD-354 were also examined using the shrew as test subject. RESULTS: Various agents with demonstrated 5-HT3 agonist properties substituted for the MD-354 stimulus (MD-354 ED50=0.5 mg/kg): quipazine (ED50=0.2 mg/kg), meta-chlorophenylbiguanide (mCPBG, ED50=1.4 mg/kg), 2-methyl 5-HT (ED50=4.5 mg/kg), 1-(2-naphthyl)biguanide (2-NBG, ED50=1.9 mg/kg), and N-(2-naphthyl)guanidine (2-NG, ED50=0.7 mg/kg). Administration of the training dose of MD-354 in combination with the 5-HT3 antagonists zacopride and tropisetron resulted in stimulus antagonism (AD50=0.02 mg/kg); administered alone, however, zacopride engendered 81% MD-354-appropriate responding (ED50=0.03 mg/kg). MD-354 was shown to produce an emetic effect in the shrew at very high doses (i.e., 40 mg/kg); however, when administered in combination with cisplatin, MD-354 behaved as an antiemetic agent at 10 mg/kg. CONCLUSION: Taken together, the results indicate that MD-354 is a 5-HT3 agonist and that it might be an agent with partial agonist activity.

Animals↗

PubMed2005

American ginseng berry extract and ginsenoside Re attenuate cisplatin-induced kaolin intake in rats.

PURPOSE: Cisplatin, a chemotherapeutic agent, causes significant nausea and vomiting. It is postulated that cisplatin-induced oxidant stress may be responsible for these symptoms. We tested whether pretreatment with American ginseng berry extract (AGBE), an herb with potent antioxidant capacity, and one of its active antioxidant constituents, ginsenoside Re, could counter cisplatin-induced emesis using a rat pica model. METHODS: In rats, exposure to emetic stimuli such as cisplatin causes significant kaolin intake, a phenomenon called pica. We therefore measured cisplatin-induced kaolin intake as an indicator of the emetic response. Rats were pretreated with vehicle, AGBE (dose range 50-150 mg/kg, IP) or ginsenoside Re (2 and 5 mg/kg, IP). Rats were treated with cisplatin (3 mg/kg, IP) 30 min later. Kaolin intake, food intake, and body weight were measured every 24 h for 120 h. Additionally, the free radical scavenging activity of AGBE was measured in vitro using ESR spectroscopy. RESULTS: A significant dose-response relationship was observed between increasing doses of pretreatment with AGBE and reduction in cisplatin-induced pica. Kaolin intake was maximally attenuated by AGBE at a dose of 100 mg/kg. Food intake also improved significantly at this dose (P<0.05). Pretreatment with ginsenoside Re (5 mg/kg) also decreased kaolin intake (P<0.05). In vitro studies demonstrated a concentration-response relationship between AGBE and its ability to scavenge superoxide and hydroxyl radicals. CONCLUSION: Pretreatment with AGBE and its major constituent, Re, attenuated cisplatin-induced pica, and demonstrated potential for the treatment of chemotherapy-induced nausea and vomiting. Significant recovery of food intake further strengthens the conclusion that AGBE may exert an antinausea/antiemetic effect.

Animals↗