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)

Oxygen-derived free radicals mediate tissue damage in acute and chronic pancreatitis. Low levels of natural antioxidants in pancreatitis indicate their increased utilization as scavengers of free radicals. Combination therapy with selenium, beta-carotene, methionine, and vitamins C and E are known to improve symptoms of chronic and recurrent pancreatitis. This, however, requires many tablets to be taken daily, which is impractical and may reduce compliance. Three patients with chronic pancreatitis (two with a history of alcohol excess and one idiopathic) are reported. Treatment with narcotic analgesics and pancreatic enzyme supplements had failed to control their symptoms. The addition of a commercially available IH636 grape seed proanthocyanidin extract (commercially known as ActiVin) to their treatment regimen led to a reduction in the frequency and intensity of abdominal pain as well as resolution of vomiting in 1 patient.
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PMID:Beneficial effects of a novel IH636 grape seed proanthocyanidin extract in the treatment of chronic pancreatitis. 1135 Nov 48

Studies have found that people with HIV have significant reductions in S-adenosylmethionine (SAMe). SAMe is an important ingredient in reactions used to make a substance that holds myelin, the coating on nerve fibers, together. SAMe also has been shown to have value in treating fibromyalgia and Alzheimer's disease. The drug may have potential use in fighting liver disease as well by increasing glutathione production and reducing the symptoms of cholestasis. Methionine, a substance made into SAMe by the body, might help improve HIV-related myelopathy. A study is currently enrolling patients with HIV to evaluate methionine's effectiveness in treating myelopathy. Side effects of methionine include nausea, vomiting, drowsiness, and irritability. Contact information is provided.
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PMID:SAMe as it ever was? 1136 83

Homocystinuria presenting as cerebral venous thrombosis is not usual. We report on a 13-year-old boy who was admitted to the hospital due to severe headache, nausea, vomiting and fever (38 degrees C). The patient was Marfan like and presented left hemiparesis and meningeal irritation sings. He was mentally retarded, had severe myopia, and had right lens dislocation one month before. Cranial CT scan was suggestive of cerebral venous infarct. MRI and magnetic resonance angiography showed venous infarcts more prominent in the right thalamic projection with hemorrhagic transformation and multiple foci of cortical (occipital and parietal bilaterally) deep parietal and left capsular bleeding, secondary of thrombosis of the transverse and sigmoid venous sinuses. High levels of homocysteine were detected in the blood and urine. Homocystinuria is an autosomal recessive inborn error of methionine metabolism caused by cystathionine-beta-synthase defect in most cases. We discuss the clinical and radiological findings in this patient, analyzing the pathophysiology of the thrombotic events related to homocystinuria.
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PMID:[Cerebral venous thrombosis and homocystinuria: case report]. 1159 91

1. Type 4 phosphodiesterase (PDE4) inhibitors mimic the pharmacological actions of alpha(2)-adrenoceptor antagonists. This has been postulated as the mechanism by which PDE4 inhibitors induce emesis and was also demonstrated by their ability to reverse xylazine/ketamine-induced anaesthesia. We further characterized this latter effect since it appears to reflect the emetic potential of PDE4 inhibitors. 2. Selective inhibitors of PDE 1, 2, 3, 4 and 5 were studied in rats, on the duration of anaesthesia induced by the combination of xylazine (10 mg kg(-1), i.m.) and ketamine (10 mg kg(-1), i.m.). PMNPQ (i.e. 6-(4-pyridylmethyl)-8-(3-nitrophenyl)quinoline) - PDE4 inhibitor: 0.01 - 3 mg kg(-1)), like MK-912 (alpha(2)-adrenoceptor antagonist: 0.01 - 3 mg kg(-1)), dose-dependently reduced the duration of anaesthesia. In contrast, vinpocetine (PDE1 inhibitor), EHNA (PDE2 inhibitor), milrinone (PDE3 inhibitor) and zaprinast (PDE5 inhibitor) had no significant effect at the doses tested (1 - 10 mg kg(-1)). Analysis of plasma and cerebrospinal fluid (CSF) of treated animals confirmed the absorption and distribution to the brain of the inactive inhibitors. 3. Neither MK-912 (3 mg kg(-1)) nor PMNPQ (0.1 - 1 mg kg(-1)) altered the duration of anaesthesia induced via a non-alpha(2)-adrenoceptor pathway (sodium pentobarbitone 50 mg kg(-1), i.p.). 4. Central NK(1) receptors are involved in PDE4 inhibitor-induced emesis. Consistently, [sar(9), Met(O(2))(11)]-substance P (NK(1) receptor agonist, 6 microg i.c.v.) reduced the duration of anaesthesia induced by xylazine/ketamine. 5. In summary, this model is functionally coupled to PDE4, specific to alpha(2)-adrenoceptors and relevant to PDE4 inhibitor-induced emesis. It therefore provides a novel way of evaluating the emetic potential of PDE4 inhibitors in rats.
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PMID:Assessing the emetic potential of PDE4 inhibitors in rats. 1178 86

The anti-emetic effects of a novel tachykinin NK(1) receptor antagonist, ezlopitant ((2S,3S-cis)-2-diphenylmethyl)- N-[(2-methoxy, 5-isopropylphenyl)methyl]-1-azabicyclo- [2.2.2]octan-3-amine), were investigated in ferrets. Ezlopitant inhibited [(3)H]substance P ([(3)H]SP) binding to the human, guinea pig, ferret and gerbil NK(1) receptors (K(i) = 0.2, 0.9. 0.6 and 0.5 nmol/l, respectively), but had no affinity to NK(2) and NK(3) receptors up to 1 micromol/l. Ezlopitant also inhibited SP-induced contraction of guinea pig trachea with a pA(2) value of 7.8, but had no effects on the baseline tension and maximum contractile response. In ferrets, ezlopitant, either orally (0.03-3 mg/kg) or subcutaneously (0.3-3 mg/kg), prevented acute retching and vomiting responses induced by intraperitoneal injection of cisplatin (10 mg/kg). In addition, repeated subcutaneous injection of ezlopitant significantly inhibited delayed retching and vomiting responses that occurred in ferrets treated with the lower dose of cisplatin (5 mg/kg, i.p.). Ezlopitant (0.1-1 mg/kg, s.c.) also produced a dose-dependent inhibition of hindpaw tapping induced by intracerebroventricular injection of [Sar(9),Met(O(2))(11)]SP in gerbils, which is known to be mediated by NK(1) receptors in the brain. These findings indicate that ezlopitant is a potent and selective NK(1) receptor antagonist, and that it inhibits both acute and delayed emetic reactions induced by cisplatin in ferrets via acting on NK(1) receptors in the central nervous system.
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PMID:Anti-emetic activity of the novel nonpeptide tachykinin NK1 receptor antagonist ezlopitant (CJ-11,974) against acute and delayed cisplatin-induced emesis in the ferret. 1237 4

Methionine tablets are used as urinary acidifiers for pets and to decrease damage from dog urine to lawns. A 39-kg Labrador Retriever ingested approximately 350 tablets containing 150 mg methionine/tablet and was presented after repeated episodes of vomiting. The only abnormality was posterior ataxia suggestive of spinal cord injury. The animal was treated with i.v. fluids, steroids and gastrointestinal protectants. Approximately 4.5 h after entering the clinic the dog had a single seizure episode lasting 2-3 min which was treated with phenobarbital. Serum ammonia at that time was normal (0.19 mg/dL). The animal did not show further CNS abnormalities and awoke apparently normal. A musty odor to the breath was noticed through the course of the day, possibly due to volatile mercaptans produced from methionine metabolism. The animal made an uneventful recovery and was discharged the next day.
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PMID:Overingestion of methionine tablets by a dog. 1464 Apr 82

Pharmacokinetics, methionine depletion, antigenicity, and toxicity of recombinant methioninase (rMETase), which has shown efficacy in achieving cell kill in a broad range of human tumor models, were examined in macaque monkeys. Dose-ranging studies at 1000, 2000, and 4000 units/kg i.v. identified the 4000 units/kg dose as able to reduce plasma methionine to an undetectable level (less than 0.5 microM) by 30 min, and the level so remained for 8 h. Pharmacokinetic analysis showed that rMETase was eliminated with a T(1/2) of 2.49 h. A 2-week i.v. administration of 4000 units/kg every 8 h/day for 2 weeks resulted in a steady-state depletion of plasma methionine to less than 2 microM. The only manifest toxicity was decreased food intake and slight weight loss. Serum albumin and red cell values declined transiently during treatment, which may be related to extensive blood sampling. Re-challenge on day 28 resulted in anaphylactic shock and death in one animal. Subsequent pretreatment with hydrocortisone prevented the anaphylactic reaction, although vomiting was frequently observed. Re-challenge was carried out at days 66, 86, and 116. Anti-rMETase antibodies (at 10(-3)) were found after the first challenge, and these increased to 10(-6) after the fourth challenge and decreased to 10(-2) by 2 months post therapy. The main rMETase antibody was IgG, and although it has some in vitro features of being a neutralizing antibody, each challenge dose was effective in depleting plasma methionine levels. Thus, rMETase was able to effectively deplete plasma methionine levels with minimal toxicity in a primate model. These data provide the bases for alteration by polyethyleneglycol conjugation (PEGylation) of the enzyme to increase its duration of effect and reduce its immunogenicity.
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PMID:Pharmacokinetics, methionine depletion, and antigenicity of recombinant methioninase in primates. 1504 34

The pharmacological properties of T-2328 were evaluated as an antagonist of the tachykinin neurokinin 1 (NK(1)) receptor. T-2328 inhibited the specific binding of [(3)H][Sar(9),Met(O(2))(11)]substance P to tachykinin NK(1) receptors in human lymphoblastic IM9 cells with K(i) of 0.08 nM. In the same assay, K(i) for aprepitant, a brain-penetrating NK(1) antagonist, was 1.3 nM. The antagonism of T-2328 is highly selective for the human NK(1) receptors since the affinities for human NK(2), NK(3) receptors, and 13 other kinds of receptors and ion channels were >1000-fold lower than for NK(1) receptors. Reduction in Bmax with no change in affinity suggests the non-competitive nature of T-2328 interaction with the NK(1) receptor. T-2328 (0.03-0.1 mg/kg, i.v.) and aprepitant (1 - 3 mg/kg, i.v.) significantly prevented the GR73632 (i.c.v.)-induced foot tapping response in gerbils. The potencies of T-2328 in both in vitro and in vivo studies were more than 10 times greater than those of aprepitant. I.v. administration of T-2328 (0.1-0.3 mg/kg) potently blocked both acute and delayed emetic responses induced by cisplatin (5 mg/kg, i.p.) in ferrets. It is concluded that T-2328 is a potent, centrally active NK(1) antagonist. T-2328 may have potential as a novel therapeutic agent for the treatment of chemotherapy-induced emesis.
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PMID:Pharmacological characterization of T-2328, 2-fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride, as a brain-penetrating antagonist of tachykinin NK1 receptor. 1818 29

A novel central nervous system (CNS) selective neurokinin-1 (NK(1)) receptor antagonist, (2S,3S)-3-[(1R)-6-methoxy-1-methyl-1-trifluoromethylisochroman-7-yl]-methylamino-2-phenylpiperidine 'CJ-17,493' (compound (+)-1), was synthesized stereoselectively using a kinetic resolution by lipase-PS as a key step. Compound (+)-1 displayed high and selective affinity (K(i)=0.2 nM) for the human NK(1) receptor in IM-9 cells, potent activity in the [Sar(9), Met(O(2))(11)]SP-induced gerbil tapping model (ED(50)=0.04 mg/kg, s.c.) and in the ferret cisplatin (10mg/kg, i.p.)-induced anti-emetic activity model (vomiting: ED(90)=0.07 mg/kg, s.c.), all levels of activity comparable with those of CP-122,721. In addition, compound (+)-1 exhibited linear pharmacokinetics rather than the super dose-proportionality of CP-122,721 and this result provides a potential solution for the clinical issue observed with CP-122,721.
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PMID:Discovery and stereoselective synthesis of the novel isochroman neurokinin-1 receptor antagonist 'CJ-17,493'. 1864 44

Several synthetic mixtures of natural and racemic crystalline amino acids suitable for the daily nitrogen requirement are tested in dogs for their tolerance upon intravenous injection. Certain mixtures of the ten essential amino acids plus non-essential amino acids exclusive of glutamic acid are accepted without any obvious sign of disturbance even at rates above 10 mg. nitrogen per kilo per minute for quantities greater than 300 mg. per kilo. One such mixture consists in parts per 100 of dl-threonine 7, dl-valine 15, l(-)-leucine 10.9, dl-isoleucine 9.9, l(+)-lysine. HCl.H(2)O 10.9, dl-tryptophane 3, dl-phenylalanine 9.9, dl-methionine 6, l(+)-histidine.HCl.H(2)O 5, l(+)-arginine-HCl 5, glycine 9.9, dl-alpha-alanine 4, dl-serine 2, l(-)-cystine 0.5, and l(-)-tyrosine 1. In addition other well tolerated mixtures included the prolines. When glutamic acid, natural or racemic, is included in similar mixtures vomiting reactions frequently occur at nitrogen rates above 4 mg. per kilo per minute. Vomiting almost always occurs on the first daily injection containing glutamic acid and usually on any subsequent injection containing more than 100 mg. glutamic acid per kilo unless given very slowly. Upon the addition of glycine certain mixtures of the ten essential amino acids show an improved tolerance. Two casein digests tested usually produced vomiting at injection rates above 2 mg. nitrogen per kilo per minute, probably because of their glutamic acid content. No serious reaction has ever occurrred to any mixture of amino acids or casein digest tested. Elimination of minor reactions such as vomiting appears possible and desirable for greater usefulness of these solutions in parenteral feeding.
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PMID:TOLERANCE TO AMINO ACID MIXTURES AND CASEIN DIGESTS GIVEN INTRAVENOUSLY : GLUTAMIC ACID RESPONSIBLE FOR REACTIONS. 1987 68


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