Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two new classes of potent 5-HT3 agents have been developed and examined as inhibitors of cytotoxic drug induced emesis in the ferret and dog. The absolute configuration of the most active molecules 10 and 18 have been determined by X-ray crystallography. These two compounds are more potent than known 5-HT3 receptor antagonists both in vivo and in vitro in blocking 5-HT3 receptor activation and preventing chemotherapeutic induced emesis. Compared with 5-HT3 antagonists, such as GR 38032F, zacopride, BRL 43694, and ICS 205-930, compound 10 was more potent in (1) inhibiting binding to 5-HT3 receptor binding sites in rat cortex (Ki = 0.17 nM), (2) blocking the von Bezold-Jarisch effect in the rat (lowest effective dose, 1 microgram/kg iv), and (3) inhibiting 5-HT-induced contraction of guinea pig ileum (lowest effective concentration, 10(-9) M). This novel agent was as effective given po as when given iv in reducing cisplatin-induced emetic episodes in the ferret (ED50 = 4 micrograms/kg iv or po). A 1 mg/kg po dose of 10 virtually abolished cisplatin-induced emesis for 10 h in the ferret. However, it was inactive against apomorphine or copper sulfate-induced vomiting. These data, coupled with receptor binding studies of ligands for D2-dopamine, a1, a2, 5-HT1, 5-HT2, and muscarinic receptors demonstrate that 10 is a highly selective 5-HT3 receptor antagonist with remarkable potency in vivo.
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PMID:Development of high-affinity 5-HT3 receptor antagonists. 2. Two novel tricyclic benzamides. 154 79

The ability of fentanyl to inhibit drug-induced emesis was investigated in the ferret. Initial studies established that morphine, in small doses (0.025-0.5 mg/kg s.c.), induced emesis in the ferret that decreased at the larger doses of 1 and 2 mg/kg (s.c.). Fentanyl (10-80 micrograms/kg s.c.) failed to induce emesis but in this dose range prevented the emesis induced by morphine (0.5 mg/kg s.c.), apomorphine (0.25 mg/kg s.c.), copper sulphate (100 mg/kg intragastric) and cisplatin (10 mg/kg i.v.). The antiemetic effects could be obtained in the absence of sedation or motor impairment. The antagonism by fentanyl of apomorphine-, copper sulphate- and cisplatin-induced emesis was inhibited by naloxone (0.1 or 0.5 mg/kg s.c.). It is concluded that fentanyl exerts a broad spectrum of actions to inhibit drug-induced emesis. An autoradiographic study of the binding of [3H]DAGO to the brainstem of the ferret indicated high densities of mu recognition sites in the area postrema, nucleus tractus solitarius, dorsal motor nucleus of the vagus, reticular medulla and other sites. The results are discussed in terms of balanced facilitatory and inhibitory opioid systems, regulating emesis and that the antiemetic actions of fentanyl reflect an important, although not necessarily an exclusive, action at mu opioid receptors.
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PMID:The actions of fentanyl to inhibit drug-induced emesis. 166 61

1. The emetic response of seven species (four genera) of frogs to apomorphine hydrochloride, copper sulfate, antimonyl potassium tartrate and mechanical stimulation at the esophageal orifice was surveyed. Xenopus laevis and Rhacophorus schlegelii were more sensitive to systemically administered apomorphine than were the other species tested. 2. The sensitivity of Rana rugosa to apomorphine varied with the season. 3. All of the species showed vigorous vomiting behavior after the oral administration of either copper sulfate or antimonyl potassium tartrate. 4. Mechanical stimulation also induced vomiting in all species. Although the species differed in sensitivity to the different emetic stimulants, the adaptive significance of this interspecific variation is not known. 5. From the stand point of the mechanics for ejecting gastric contents, there is little difference between frogs and mammals. 6. Frogs, particularly Xenopus laevis, may be a useful non-mammalian model for studying emesis.
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PMID:Interspecific variation in the emetic response of anurans. 168 29

The effect of acute ethanol administration into the cerebral ventricles of the unanesthetized cat upon emesis produced by norepinephrine and nicotine injected similarly was investigated. Ethanol inhibited the norepinephrine- and nicotine-induced emesis. The inhibitory effect of ethanol occurred after a transient and inconsistent emetic action of the drug. Ethanol was about 10 times more potent inhibiting the emesis caused by nicotine. On the other hand, intracerebroventricular ethanol had virtually no effect on emesis produced by intragastric copper sulfate. The inhibitory effect of ethanol is ascribed to an action on alpha-noradrenergic and nicotinic receptors in the area postrema. Differential responses to ethanol most probably reflect the microenvironment of alpha-noradrenergic and nicotinic synapses in the area postrema of the cat.
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PMID:Selective effect of ethanol on norepinephrine- and nicotine-induced emesis in cats. 178 27

YM060, (R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride, is a new serotonin (5HT)3-receptor antagonist. We examined the effects of YM060 on chemotherapeutic agent-, apomorphine- and copper sulfate-induced emesis. Intravenous YM060 potently prevented cisplatin (10 mg/kg, i.v.)-induced emesis with ED50 values of 0.06 (0.05-0.07) micrograms/kg, i.v. in ferrets. Based on the ED50 values, YM060 was 300, 20 and 100 times more potent than ondansetron, granisetron and the S-isomer of YM060, respectively. The relative potencies of these drugs described above were similar to those in the previously reported 5HT3-receptor antagonism. YM060 given orally also potently inhibited cisplatin (10 mg/kg, i.p.)- and cyclophosphamide (200 mg/kg, i.p.)-induced emesis in ferrets with ED50 values of 0.1 (0.09-0.11) and 0.02 (0.16-0.27) micrograms/kg, p.o., respectively. All tested 5HT3-receptor antagonists including YM060 failed to prevent apomorphine (0.1 mg/kg, s.c.)-induced emesis in dogs and copper sulfate (1%, 10 ml, p.o.)-induced emesis in ferrets. Our data indicate that YM060 is a highly potent inhibitor of chemotherapeutic agent-induced emesis and that the antiemetic effect of YM060 may be depend on 5HT3-receptor antagonism.
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PMID:Antiemetic effects of YM060, a potent and selective serotonin (5HT)3-receptor antagonist, in ferrets and dogs. 181 64

5 major criteria are used to evaluate family planning methods: efficacy, both theoretical and practical; acceptability as measured by continuation of use; safety; reversibility; and cost, including the cost of treatment, follow-up, and screening for contraindications. Traditional family planning methods are mostly based on periodic abstinence during the presumed fertile period. The calendar, temperature, Billings or cervical mucus, and symptothermal methods are based on observation of different symptoms of ovulation and fertility. Their advantages are that they do not require intervention by health personnel, their costs of use are nil, and they are morally acceptable to some couples. Their efficacy is lower than that of other methods and they should be viewed as methods to space rather than limit births. The withdrawal method, also less effective, requires active cooperation by the male partner. Among mechanical methods, the use of condoms has increased recently because of the protection they offer against HIV infection and other sexually transmitted diseases. Their efficacy depends on correct use, regular use, and the quality of the condom. The Pearl index varies from 93099 per 100 woman-years. The diaphragm must be individually measured and should be used with spermicides. The Pearl index ranges from 85095 per 100 woman-years. Spermicides, generally either nonoxynol-9 or benzalkonium chloride, are surfactants that have a Pearl index of 83-97 per 100 woman-years. They are available as creams, jellies, foams, suppositories, tablets, or impregnated sponges. Most failures appear due to errors of utilization. The mechanism of action of the IUD is imperfectly understood, but it is known to prevent nidation of the fertilized egg. Copper devised have higher rates of efficacy and tolerance. Pearl indices range from 95-99.5. Contraindications include genital infection, uterine anomalies, valvular cardiopathy, and coagulation problems. The IUD is relatively contraindicated if there is history of ectopic pregnancy or upper genital tract infections. The combined oral contraceptive is the most widely utilized method in France. The Pearl index is nearly 100 in the absence of forgetting, vomiting, or drug interactions. The contraindications are basically those of estrogens: history of thrombosis, prolonged bedrest, hypertension, hyperlipidemia, hepatic disorders, hormonodependent cancers, or smoking after age 35. Progestin-only methods are available in 3 forms: low-dose pills which must be taken at the same time each day, higher-dosed progestins taken for 20 days each month, and injectable progestins providing contraception for 8-12 weeks. Postcoital contraception using OCs or IUDs is possible but not well known among women or physicians. The Neuwirth law authorizing use of contraception in France was passed in 1967. Amendments in 1974 improved access and provided for reimbursement for some methods, but some newer forms are not reimbursed.
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PMID:[Family planning. Objectives, measures, regulations, structures]. 185 35

The intravenous injection of cisplatin (10 mg/kg), the subcutaneous injection of apomorphine (0.125-1 mg/kg) and lisuride (0.001-0.1 mg/kg), the oral administration of ipecacuanha (0.3-2.4 mg/kg) and the intragastric administration of copper sulphate (25-100 mg/kg), induced a vomiting and retching response in the ferret. Pretreatment with dl-fenfluramine (5 mg/kg i.p.) prevented or reduced the emesis induced by cisplatin, apomorphine, ipecacuanha and lisuride but failed to significantly antagonise copper sulphate-induced emesis. The 5-HT3 receptor antagonist ICS 205-930 (0.1 mg/kg i.p.) prevented emesis induced by cisplatin and ipecacuanha but failed to prevent or significantly reduce the emesis induced by apomorphine, lisuride or copper sulphate. Dopamine receptor antagonists, including fluphenazine (0.1-1.0 mg/kg i.p.) prevented apomorphine- and lisuride-induced emesis but were less potent or had inconsistent actions to antagonise cisplatin- or ipecacuanha-induced emesis and failed to inhibit the emesis induced by copper sulphate. The data indicate that dopamine and/or 5-HT3 receptor systems are involved in drug-induced emesis but that emesis caused by gastric irritation induced by copper sulphate is mediated by different receptor mechanisms.
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PMID:Fluphenazine, ICS 205-930 and dl-fenfluramine differentially antagonise drug-induced emesis in the ferret. 197 49

Antiemetic effects of serotonin 5-HT3 receptor antagonists (ICS205-930, zacopride, BRL43694, GR38032F) were investigated in Suncus murinus. Veratrine, nicotine, copper sulfate, cisplatin, cyclophosphamide and motion sickness were used as emetic stimuli. Serotonin 5-HT3 receptor antagonists did not inhibit emetic responses to veratrine, nicotine, copper sulfate and motion sickness. However, cisplatin- and cyclophosphamide-induced emesis was strongly blocked by them. Both subcutaneous and intravenous injections of 5-HT3 antagonists were effective. Serotonin 5-HT1 and 5-HT2 receptor antagonists were less effective. These results clearly indicate that a 5-HT3 receptor-mediated mechanism(s) is involved in the emesis caused by cancer chemotherapeutic agents and that 5-HT3 receptor antagonists are very effective as prophylactic drugs.
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PMID:Selective blockade of cytotoxic drug-induced emesis by 5-HT3 receptor antagonists in Suncus murinus. 204 Dec 20

The methods known to be practical for post-ovulatory contraception, defined as any substance or device used after coitus to prevent establishment of pregnancy up to 14 days after ovulation are reviewed. Most are used only in emergency for a single episode of unprotected intercourse or failed contraception, exceptions being the "visiting pill" of norethindrone used for migrant workers in China, and the IUD when inserted for this purpose as well as ongoing contraception. The physiology of ovulation, fertilization, transport of the ovum, and implantation of the blastocyst are reviewed. Estimates of the odds of becoming pregnant after an isolated unprotected intercourse range from 10-25%. High-dose estrogens, either stilbestrol (no longer used in the U.S.), ethinyl estradiol 5 mg, or conjugated estrogens 30 mg, have been used since early trials in the 1960s. Estrogen must be given for 5 days, started within 72 hours of coitus, and cause several unpleasant side effects, notably nausea, vomiting, mastalgia, and menstrual irregularity. Although no incidents have been reported, they are contraindicated for those at risk of thromboembolism. The failure rate is about 0.7%. Combined estrogen and progestagen, known as the Yuzpe method, consists of 2 dose of 100 mcg ethinyl estradiol and 1 mg norgestrel, repeated in 12 hours. The reported failure rates range from 0.2%-7.4%. Insertion of a copper IUD is effective post-coitally within 66 days, with failure rate less than 0.1%. The antiestrogen Danazol, which actually acts as an antigonadotrophin, can be used as a postcoital agent, in divided doses of 800 or 1200 mg 12 hours apart within 72 hours of exposure. Published failure rates are 2.5 and 0.9% with these doses. Progestagens alone have been studied by WHO, but failure rates were as high as 10.1% in women with frequent intercourse. Regular use was not recommended since cycles became unpredictable. Studies are being conducted on RU-486 and prostaglandins for postcoital use, in comparison with the Yuzpe regimen. A true luteolytic agent for women would seem to be the perfect postcoital agent, yet none exist.
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PMID:Post-ovulatory contraception. 222

Preceding vomiting, several changes in small intestinal motility have been described. They consist mainly of high-amplitude retrograde contractions and inhibition of motility before and after these contractions. The recordings of 94 episodes of emesis occurring spontaneously, during manometric studies of intestinal motility by means of infused catheters in dogs with gastric and duodenal cannulae, showed that 95.7% of all episodes developed during phase II of the migratory motor complex. In order to establish whether different phases of the fasting cyclic activity are associated with a different sensitivity to emetic stimulus, two agents, apomorphine, a centrally acting drug and copper sulfate, a peripherally acting agent, were administered at the beginning of phases I and II of the migratory motor complex. Coincident with spontaneously occurring vomiting, a statistically significative greater number of responses to both emetic agents was observed during phase II as compared to phase I. This finding suggests that cyclic changes of the small bowel motility are related to changes in the threshold of the vomiting center.
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PMID:Relationship between small intestinal fasting motility and vomiting in dogs. 230 87


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