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)

Pharmacological and biochemical properties of a novel compound, N-(1-benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-08050) were compared with those of haloperidol (HPD) and chlorpromazine (CPZ) in animals. YM-08050 was more potent than either HPD or CPZ in inhibitory effects on a variety of behaviors such as apomorphine-induced stereotypes behavior and emesis, methamphetamine-induced stereotyped behavior, conditioned avoidance response and open field behavior. YM-08050 induced catalepsy only at much higher doses than to exhibit the inhibitory activities. The inhibitory effects of YM-08050 on [3H]dopamine binding and dopamine-sensitive adenylate cyclase in the synaptic membrane fractions of canine caudate nucleus were much greater than those of HPD and CPZ. The results suggest that YM-08050, a potent central dopaminergic blocker, is a potential antipsychotic drug with less extrapyramidal side effects than those of HPD and CPZ.
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PMID:Pharmacological and biochemical studies on a new potential neuroleptic, N-(1-benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-08050). 4 18

Based on positive results in laboratory animals, chlorpromazine was given a clinical trial in humans to determine if it could reduce fluid losses during cholera. In animals, the chlorpromazine inhibited cholera toxin-stimulated intestinal adenylate cyclase and fluid secretion. Therefore, 11 cholera patients suffering severe diarrhea (360-1340 ml/hour) and vomiting were given either intramuscular chlorpromazine (1 mg/kg or 4 mg/kg) (n=8) or oral chlorpromazine of the same dose (1 mg/kg) (n=3). Overall reduction in stool output of 66% in the treated patients was evident after 32 hours of treatment. The decrease in treated patients was significantly greater than the reduction in nontreated patients (26%) during the same 32-hour course of illness. Patients' comfort was also enhanced by the decrease in nausea and mild sedative qualities of chlorpromazine, and no hypotension was observed in these well-hydrated patients.
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PMID:Chlorpromazine reduces fluid-loss in cholera. 8 63

A new peripheral dopamine agonist which causes dopaminergic renal vasodilation, was tested for central dopaminergic activity. SK & F 38393 stimulated the dopamine-sensitive adenylate cyclase in homogenates of rat caudate, as a partial agonist, and caused contralateral rotation in rats with unilateral 6-OHDA lesions of substantia nigra. Rotation was shown to be due to a direct effect on supersensitive dopamine receptors. Stimulation of cAMP formation and rotation were blocked by dopamine antagonists. In contrast to other dopamine agonists, SK & F 38393 did not cause stereotypy, emesis or inhibition of prolactin release, nor did SK & F 38393 affect dopamine turnover. The results suggest that SK & F 38393 may selectively stimulate supersensitive central dopamine receptors in vivo or may activate only a certain subclass of dopamine receptors including the receptor in the renal vasculature and the adenylate cyclase coupled postsynaptic receptor in the caudate.
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PMID:The central effects of a novel dopamine agonist. 56 69

Piflutixol, 6-fluoro-9-[3-(4-(2-hydroxyethyl)piperidino)propylidene]-2-trifluoromethyl-thioxanthene, has been shown to have pronounced neuroleptic properties. It is a very potent inhibitor of methylphenidate-induced stereotypies in mice, amphetamine and apomorphine-induced stereotypies in rats, apomorphine-induced stereotypies and vomiting in dogs. Furthermore piflutixol causes cataleptic reaction in small doses and inhibits conditioned avoidance reaction in rats. The compound is equally potent orally and parenterally and has a prolonged effect. Piflutixol has up to the present proved to be the most potent inhibitor of dopamine-stimulated adenylate cyclase in rat striatum in vitro. Piflutixol has a stron sedative effect (inhibition of spontaneous motor activity, induction of ptosis and potentiation of barbiturate anaesthesia) and in addition inhibits reticular arousal reaction in very low doses. Thus piflutixol constitutes a unique combination of potent anti-stereotyped activity with potent sedative effects. This means that piflutixol may prove to be a low-dose basic neuroleptic with long duration of action.
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PMID:The pharmacology of a new potent, long acting neuroleptic, piflutixol. 57 63

Evidence is presented for the existence of three distinct enterotoxins detected in concentrated cell-free culture filtrates of selected Bacillus cereus strains. The first was a product capable of stimulating the adenylate cyclase-cyclic-AMP system in intestinal epithelial cells and, possibly through this, causing fluid accumulation in ligated ileal sections ("loops") of young rabbits. This was elaborated by a strain isolated from an incident of diarrhoea and which caused diarrhoea in 6 of 10 monkey feedings. The second was tentatively identified as a factor which caused fluid accumulation in rabbit loops but not, apparently, through stimulation of the adenylate cyclase-cyclic-AMP system; this was elaborated by a strain isolated from raw rice which failed to produce symptoms in eight monkey feedings. Together, the behaviour of these two factors indicates that diarrhoea caused by B. cereus enterotoxin may be a cyclic-AMP-mediated event. The third, here referred to as "pyogenic toxin", caused severe tissue damage in the ileal mucosa and was elaborated by a strain isolated from a brain abscess. A factor produced by a strain isolated from an outbreak of vomiting which caused vomiting in 10 of 24 monkey feedings could bot be detected in tests reported here but appears to be a fourth enterotoxin type. Cytopathic effects in tissue cultures, suckling mouse tests, and assays of glycerol production by fat cells were not found to be of value in the detection of any of the enterotoxins.
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PMID:Studies on the production of enterotoxins by Bacillus cereus. 82 25

Infants and young children are particularly susceptible to a recently identified viral enteritis which is highly contagious and seems both common and universal. In this disease, virus invades the upper intestinal epithelium, causing acute diarrhoea with early fever and vomiting. We studied a similar disease in pigs, infecting three-week-old animals with transmissible gastroenteritis virus (TGE), which also invades the upper intestinal epithelium. In this model, diarrhoea is massive 16-40 hours after infection, when stools contain increased electrolytes but no excess of sugar. In the jejunum of intact pigs at the 40-hour stage we found altered Na+ and water flux, decreased mucosal activities of disaccharidases and Na+, K+-ATPase, but normal adenylate cyclase activity. At the same stage the response of Na+ flux to glucose was blunted in jejunal epithelium studied in Ussing short-circuit chambers and in suspensions of villous cells; Cl- flux responded normally to theophylline, and thymidine kinase and sucrase activities of cells isolated from jejunal villi were similar to those found in crypt cells. Probably by 40 hours after infection most virus has been shed from the mucosa. Viral diarrhoea clearly differs from enterotoxigenic diarrhoea. Consideration of its pathogenesis must take into account the dynamic nature of the mucosal epithelium and the factors governing differentiation of enterocytes as they migrate from crypt to villus. Sufficient information is available now to characterize one specific and apparently prevalent viral enteritis in man and to identify additional viral enteritides. There is hope that preventative therapy can be developed. Our understanding of the mechanisms of viral diarrhoea is limited, but the availability of an animal model and the promise of others makes us optimistic that these deficiencies can be remedied. Greater understanding of the pathogenesis of viral diarrhoea should better the active therapy of affected infants and children.
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PMID:Viral gastroenteritis: recent progress, remaining problems. 104 55

1. Multiple-barreled microelectrodes were used to record from neurons in the area postrema of anesthetized dogs and to test the responses of the neurons to a variety of substances in this structure, which is known to function as the chemoceptive trigger zone for emesis. 2. The neurons in area postrema were silent at rest but could be "found" by virtue of their response to ionophoretic glutamate. The glutamic response was brief and of short latency with high frequency of discharge. 3. Dog area postrema neurons were also excited by over 20 other substances, including acetylcholine, the biogenic amines, several peptides, and at least two hormones. Not all agents were excitatory, however. 4. The responses to all excitatory agents except glutamate were similar and unusual. All responses showed a relatively long latency (3-20 s), a long duration of excitation (30 s to many minutes), and a low discharge frequency (1-3 Hz). 5. There was a good correlation between substances that were excitatory on area postrema neurons and substances known to cause emesis. Because emesis due to intravenous application of these substances is known to be abolished in animals with ablation of the area postrema, it is very likely that recordings were from the neurons which trigger the response. 6. Because so many substances elicit the same type of response there is a possibility that all utilize a common second messenger. Neurons were not excited by ionophoresis of guanosine 3',5'-cyclic monophosphate (cGMP) but were excited by 8-bromo-adenosine 3',5'-cyclic monophosphate (cAMP) and by forskolin, an activator of adenylate cyclase. 7. Behavioral studies were performed looking for emetic responses in awake dogs following intravenous injection of apomorphine, insulin, angiotensin II, and leucine enkephalin. For each a threshold concentration could be determined, which would consistently evoke emesis. 8. Dogs pretreated with phosphodiesterase inhibitors (theophylline, 3-isobutyl-1-methylxanthine, or RO 1724) showed a shift in the threshold concentration of the above substances that triggered emesis, such that emesis was evoked by lower concentrations than in the control. 9. These results suggest that neurons of the dog area postrema trigger the emetic reflex in response to specific receptors for a great variety of transmitters, peptides, and hormones, and that these receptors act through a common second messenger, cAMP.
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PMID:Excitation of area postrema neurons by transmitters, peptides, and cyclic nucleotides. 289 67

SCH39166 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl- 5H-benzo[d]naptho-(2,1-b)azepine] is a benzonaphthazepine that has been evaluated as a selective D1 dopamine receptor antagonist. In vitro, SCH39166 (Ki = 3.6 nM) inhibited the binding of [3H]SCH23390 (a D1 specific compound) and blocked dopamine-stimulated adenylate cyclase (Ki = 9.1 nM); in contrast the Ki for SCH39166 to displace [3H]spiperone (D2) was greater than 1 microM and its Ki vs. [3H]-ketanserin (5-hydroxytryptamine2) binding was greater than 300 nM. In vivo, SCH39166 inhibited both rat and squirrel monkey conditioned avoidance responding (minimal effective dose = 10 and 1.78 mg/kg p.o., respectively) and had a duration of at least 6 hr in both species. In addition, SCH39166 antagonized apomorphine-induced stereotypy in rats (minimal effective dose = 10 mg/kg p.o.). These in vivo actions of SCH39166 are similar to the activity of typical dopamine antagonists. However, in contrast to D2-selective antagonists, SCH39166 failed to increase plasma prolactin levels, did not block apomorphine-induced emesis in the dog and had minimal effects on the striatal levels of homovanillic acid or dihydroxyphenylacetic acid. Furthermore, although immobility was seen after p.o. administration of SCH39166 using the inclined screen test, the drug did not cause catalepsy at doses up to 10 times its minimal effective dose in the rat conditioned avoidance response test. Additionally, SCH39166 inhibited apomorphine-induced climbing at lower doses than it inhibited apomorphine-induced sniffing in mice. The results from these latter two tests suggest that SCH39166 may have a reduced liability to produce extrapyramidal side effects. Therefore, based on this profile of activity, SCH39166 is a selective D1 dopamine receptor antagonist both in vitro and in vivo. Additionally, because this compound is longer acting in the primate than previously available D1 antagonists, it has potential utility as a clinically useful drug.
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PMID:Pharmacological profile of SCH39166: a dopamine D1 selective benzonaphthazepine with potential antipsychotic activity. 290 2

A new benzamide, cis-N-(1-benzyl-2-methylpyrrolidin - 3 - yl) - 5 - chloro - 2 - methoxy - 4 - methylaminobenzamide (YM-09151-2) exhibited more potent and longer-lasting inhibitory effects on apomorphine-induced behaviours (stereotyped behaviour, emesis and hypothermia), and methamphetamine-induced stereotyped behaviour, conditioned avoidance response and open field behaviour, conditioned avoidance response and open field behaviour than either structurally similar benzamides (YM-0850 and sulpiride) or classical neuroleptics [chlorpromazine (CPZ) and haloperidol(HPD)]. Such inhibitory effects of YM-09151-2 relative to cataleptogenicity were greater than those of CPz and HPD. In contrast, sulpiride elicited few of the neuroleptic effects described above. YM-09151-2, a potent inhibitor for dopamine-sensitive adenylate cyclase (Ki: 3.0 nM) reduced, in a selective manner, the binding of [3H]dopamine to the dopamine D1 receptor (Ki:4.8 nm) associated with adenylate cyclase rather than to the dopamine D2 receptor (Ki: 0.98 microM) independent of adenylate cyclase. Sulpiride, on the contrary, inhibited only the binding to the dopamine D2 receptor, CPZ and HPD antagonized [3H]dopamine nonselectively at the two distinct dopaminergic receptors. These results suggest that YM-09151-2 is a potent and long-lasting neuroleptic with a highly selective blocking action on the dopamine D1 receptor.
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PMID:Neuroleptic properties of cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-09151-2) with selective antidopaminergic activity. 611 70

SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol) possesses pharmacologic effects similar to standard antipsychotics, including selective supression of conditioned avoidance responding in rats and squirrel monkeys, blockade of apomorphine-induced stereotypy in rats and blockade of methamphetamine-induced lethality in aggregated mice. At effective doses in these tests, no changes in gross behavior, neurological or autonomic function were observed. In contrast to the standards tested, SCH 23390 blocked dopamine-stimulated adenylate cyclase at concentrations (IC50 = 0.01 microM) about 2000 times lower than those needed to block spiperone binding (IC50 = 24 microM). This suggests specific D1-receptor antagonism. Inability of SCH 23390 to cause hyperprolactinemia, considered to be a D2-receptor effect, is consistent with this hypothesis. SCH 23390 showed lower increases in dopamine turnover suggesting that the blockade of SCH 23390 may be more specific for post- than presynaptic sites. Additional evidence for the selectivity of SCH 23390 among putative postsynaptic dopamine sites includes its lack of effect on apomorphine-induced hypothermia or emesis. Based on these results, it is postulated that SCH 23390 is a selective D1-receptor antagonist.
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PMID:SCH 23390, a potential benzazepine antipsychotic with unique interactions on dopaminergic systems. 613 95


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